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(7-methoxycoumarin-4-yl)acetyl-KLVFFAEDK(Dnp)-OH + H2O
?
fluorogenic substrate derived from the reported Abeta1-40 core peptide cleavage sequence. The R183Q mutant enzyme exhibits significantly decreased rate of fluorogenic peptide hydrolysis, yet retains similar binding affinity by comparison with the wild-type enzyme
-
-
?
(7-methoxycoumarin-4-yl)acetyl-NPPGFSAFK-2,4-dinitrophenyl + H2O
?
-
bradykinin mimetic substrate V
-
-
?
(7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH + H2O
?
-
-
-
?
(7-methoxycoumarin-4-yl)acetyl-RPPGFSAFK(2,4-dinitrophenyl)-OH + H2O
?
-
-
-
?
(7-methoxycoumarin-4-yl)acetyl-RPPGFSAFK-2,4-dinitrophenyl + H2O
?
(7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH + H2O
?
-
-
-
?
2-amino-benzoyl-GGFLRKAGQ-ethylenediamine-2,4-dinitrophenyl + H2O
?
-
-
-
?
2-amino-benzoyl-GGFLRKHGQ-ethylenediamine-2,4-dinitrophenyl + H2O
?
-
-
-
?
2-amino-benzoyl-GGFLRKMGQ-ethylenediamine-2,4-dinitrophenyl + H2O
?
-
-
-
?
2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine) + H2O
?
2-aminobenzoyl-GGFLRKHGQ-ethylenediamine-2,4-dinitrophenyl + H2O
2-aminobenzoyl-GGFLR + KHGQ-ethylenediamine-2,4-dinitrophenyl
-
-
-
-
?
7-methoxycoumarin-4-yl-acetyl-RPPGF-SAFK-2,4-dinitrophenyl + H2O
?
-
-
-
?
7-methoxycoumarin-4-yl-acetyl-RPPGFSAFK-2,4-dinitrophenyl + H2O
?
7-methoxycoumarin-4-ylacetyl-NPPGFSAFK-2,4-dinitrophenyl + H2O
?
-
-
-
-
?
Abz-GFLRKGVQ-EDDnp + H2O
?
-
-
-
-
?
Abz-GGFLRKHGQ-EDDnp + H2O
?
-
-
-
?
Abz-GGFLRKHGQ-EDDnp + H2O
Abz-GGFLR + KHGQ-EDDnp
Abz-Gly-Gly-Leu-Arg-Lys-His-Gly-Gln-EDDnp + H2O
?
-
-
-
?
Abz-SEKKDNYIIKGV-nitroY-OH + H2O
?
-
a substrate based on the polypeptide sequence of the yeast P2 a-factor mating propheromone
-
-
?
amylin + H2O
amylin peptide fragments
amyloid alpha-peptide + H2O
?
-
-
-
?
amyloid beta + H2O
amyloid beta peptide fragments
amyloid beta peptide + H2O
?
amyloid beta peptide 1-40 + H2O
?
-
physiolgical substrate
-
?
amyloid beta-peptide (Abeta1-40) + H2O
?
recombinant R183Q mutant enzyme is less active than the recombinant wild-type enzyme against recombinant amyloid beta-peptide (Abeta1-40)
-
-
?
amyloid beta-peptide + H2O
?
amyloid beta-peptide 1-40 + H2O
?
amyloid beta-peptide 1-42 + H2O
?
-
cleavage occurs at peptide bonds Phe19-Phe20, Phe20-Ala21, and Leu34-Met35, with the latter cleavage site being the initial and principal one
-
?
amyloid beta-peptide(1-40) + H2O
?
-
-
-
?
amyloid beta-peptide1-40 + H2O
?
degradation
-
-
?
amyloid beta-protein + H2O
?
amyloid beta-protein A21G + H2O
?
-
Flemish genetic variant
-
-
?
amyloid beta-protein E22K + H2O
?
-
Italian genetic variant
-
-
?
amyloid beta-protein E22Q + H2O
?
-
Dutch genetic variant
-
-
?
amyloid beta1-40 + H2O
?
-
-
-
-
?
amyloid beta40 + H2O
amyloid beta40 peptide fragments
amyloid beta42 + H2O
amyloid beta42 peptide fragments
amyloid peptide + H2O
?
-
23 amino acid peptide resulting from internal proteolysis of wild-type type 2 transmembrane protein BRI2
-
-
?
amyloid peptide ABri + H2O
?
-
34 amino acid peptide resulting from internal proteolysis of genetically defect type 2 transmembrane protein BRI2 in patients with familial British dementia. Enzymic degradation of peptide is more efficient with monomeric peptide than with aggregated peptide
-
-
?
amyloid peptide ADan + H2O
?
-
34 amino acid peptide resulting from internal proteolysis of genetically defect type 2 transmembrane protein BRI2 in patients with familial Danish dementia
-
-
?
amyloid-beta peptide + H2O
?
angiotensin + H2O
?
-
-
-
?
ATP + H2O
ADP + phosphate
Atrial natriuretic factor + H2O
?
atrial natriuretic peptide + H2O
?
-
-
-
?
ATTO 655-Cys-Lys-Leu-Val-Phe-Phe-Ala-Glu-Asp-Trp + H2O
?
-
-
-
?
beta-amyloid (Abeta)1-40 + H2O
?
-
-
-
?
beta-amyloid peptide + H2O
?
-
-
-
?
beta-amyloid precursor protein intracellular domain + H2O
?
-
-
-
?
beta-amyloid protein + H2O
?
beta-endorphin + H2O
gamma-endorphin + ?
calcitonin + H2O
?
-
-
-
?
CH3NH-Ala-Ala-Ala-CONHCH3 + H2O
?
-
energetic profile of proteolysis mechanism of IDE
-
-
?
CH3NH-Leu-Tyr-Leu-CONHCH3 + H2O
?
-
energetic profile of proteolysis mechanism of IDE
-
-
?
Dabcyl-Tyr-Glu-Val-His-His-Gln-Lys-Leu-Val-Phe-Phe-Ala-Glu-Asp-Val-Gly-Glu(EDANS)-NH2 + H2O
?
-
fluorogenic derivative of amyloid beta containing residues 10-25
-
-
?
desalanine-insulin + H2O
?
-
-
-
-
?
desdipeptide-proinsulin + H2O
?
-
-
-
-
?
desnonapeptide-proinsulin + H2O
?
-
-
-
-
?
destridecapeptide-proinsulin + H2O
?
-
-
-
-
?
dynorphin A-17 + H2O
?
-
-
-
?
dynorphin B-13 + H2O
?
-
-
-
?
dynorphin B-9 + H2O
?
-
-
-
?
dynorphin B9 + H2O
?
-
-
-
?
epidermal growth factor + H2O
epidermal growth factor peptide fragments
-
identification of cleavage sites by mass spectrometry and NMR
-
-
?
Fragment of cytochrome c + H2O
Hydrolyzed fragment of cytochrome c
-
Ile81-Glu108
cleavage at Tyr97-Leu98 bond
?
glucagon + H2O
glucagon peptide fragments
-
-
-
-
?
Glucagon + H2O
Hydrolyzed glucagon
haemoglobin + H2O
?
-
damaged haemoglobin oxidatively degraded
-
?
InsL3 + H2O
InsL3 fragments
Insulin + H2O
Hydrolyzed insulin
insulin + H2O
insulin fragments
insulin + H2O
insulin peptide fragments
Insulin growth factor II + H2O
?
insulin-like growth factor I + H2O
insulin-like growth factor I peptide fragments
insulin-like growth factor II + H2O
insulin-like growth factor II peptide fragments
insulin-like growth factor-II + H2O
insulin-like growth factor-II peptide fragments
-
identification of cleavage sites by mass spectrometry and NMR
-
-
?
insulin-like peptide 3 + H2O
processed insulin-like peptide 3 + WSTEA
islet amyloid polypeptide + H2O
?
kallidin + H2O
?
-
cleavage at Pro/Phe site
-
-
?
Lysozyme + H2O
?
-
degradation of oxidatively damaged lysozyme
-
?
monoarginine-insulin + H2O
?
-
-
-
-
?
o-aminobenzoic acid-GGFLRKHGQ-ethylenediamine-2,4-dinitrophenyl + H2O
?
-
-
-
?
Oxidatively damaged hemoglobin + H2O
?
peptide containing the mitochondrial targeting sequence of E1alpha subunit of human pyruvate dehydrogenase + H2O
?
-
hydrolysis occurs at several sites
-
-
?
Porcine proinsulin intermediates + H2O
?
-
cleaved proinsulin, desdipeptide-proinsulin, desnonapeptide-proinsulin, destridecapeptide-proinsulin, desalanine-insulin, monoarginine-insulin and diarginine-proinsulin are degraded at 19.8%, 25.6%, 63.5%, 73.7%, 101.5%, 98% and 98% of the activity of insulin, respectively
-
-
?
Proinsulin + H2O
Hydrolyzed proinsulin
-
15fold greater rate of insulin destruction over that for proinsulin
-
-
?
protein ANP + H2O
?
-
-
-
-
?
protein BNP + H2O
?
-
-
-
-
?
protein CNP + H2O
?
-
-
-
-
?
protein DNP + H2O
?
-
-
-
-
?
reduced amylin + H2O
reduced amylin peptide fragments
-
identification of cleavage sites by mass spectrometry
-
-
?
relaxin + H2O
relaxin fragments
relaxin-3 + H2O
relaxin-3 fragments
Transforming growth factor + H2O
?
transforming growth factor alpha + H2O
?
-
-
-
?
transforming growth factor-alpha + H2O
transforming growth factor-alpha peptide fragments
-
identification of cleavage sites by mass spectrometry
-
-
?
Tryptic fragment of bovine serum albumin + H2O
Hydrolyzed tryptic fragment of bovine serum albumin
-
Leu503-Lys518
cleaved at Phe506-His507
?
ubiquitin + H2O
?
-
IDE cleaves ubiquitin in a biphasic manner, first, by rapidly removing the two C-terminal glycines (kcat = 2/sec) followed by a slow cleavage between residues 72-73 (kcat = 0.07/sec), thereby producing the inactive Ub1-74 and Ub1-72
-
-
?
urodilatin + H2O
?
-
-
-
-
?
[(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH + H2O
[(7-methoxycoumarin-4-yl)acetyl]-RPPGF + SAFK(Dnp)-OH
additional information
?
-
(7-methoxycoumarin-4-yl)acetyl-RPPGFSAFK-2,4-dinitrophenyl + H2O
?
-
-
-
-
?
(7-methoxycoumarin-4-yl)acetyl-RPPGFSAFK-2,4-dinitrophenyl + H2O
?
-
-
-
?
2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine) + H2O
?
-
-
-
-
?
2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine) + H2O
?
-
-
-
-
?
7-methoxycoumarin-4-yl-acetyl-RPPGFSAFK-2,4-dinitrophenyl + H2O
?
-
-
-
?
7-methoxycoumarin-4-yl-acetyl-RPPGFSAFK-2,4-dinitrophenyl + H2O
?
-
fluorogenic bradykinin-mimetic IDE substrate V
-
-
?
Abz-GGFLRKHGQ-EDDnp + H2O
Abz-GGFLR + KHGQ-EDDnp
-
substrate or small peptide activation occurs through a cis effect
-
-
?
Abz-GGFLRKHGQ-EDDnp + H2O
Abz-GGFLR + KHGQ-EDDnp
-
-
-
-
?
Abz-GGFLRKHGQ-EDDnp + H2O
Abz-GGFLR + KHGQ-EDDnp
-
synthetic fluorogenic substrate
-
-
?
amylin + H2O
?
-
-
-
?
amylin + H2O
?
-
degradation
-
-
?
amylin + H2O
?
-
degradation
-
-
?
amylin + H2O
?
-
degradation
-
-
?
amylin + H2O
amylin peptide fragments
-
-
-
-
?
amylin + H2O
amylin peptide fragments
-
identification of cleavage sites by mass spectrometry and NMR. The presence of a disulfide bond in amylin allows IDE to cut at an additional site in the middle of the peptide, amino acids 18-19, binding structure, overview
-
-
?
amyloid beta + H2O
?
-
-
-
?
amyloid beta + H2O
?
-
-
-
-
?
amyloid beta + H2O
?
role of insulin-degrading enzyme in the intracytosolic clearance of amyloid beta and other amyloid-like peptides
-
-
?
amyloid beta + H2O
amyloid beta peptide fragments
-
-
-
-
?
amyloid beta + H2O
amyloid beta peptide fragments
-
-
-
-
?
amyloid beta peptide + H2O
?
-
-
-
-
?
amyloid beta peptide + H2O
?
-
the catalytic mechanisms for the hydrolysis of the three different peptide bonds (Lys28-Gly29, Phe19-Phe20, and His14-Gln15) of amyloid beta peptide is determined: For all these peptides, the nature of the substrate is found to influence the structure of the active enzyme-substrate complex. (1) activation of the metal-bound water molecule, (2) formation of the gem-diol intermediate, and (3) cleavage of the peptide bond. The process of water activation is found to be the rate-determining step for all three substrates
-
-
?
amyloid beta peptide + H2O
?
-
-
-
-
?
amyloid beta peptide + H2O
?
-
-
-
?
amyloid beta peptide + H2O
?
-
-
-
-
?
amyloid beta-peptide + H2O
?
-
-
-
?
amyloid beta-peptide + H2O
?
-
-
-
-
?
amyloid beta-peptide + H2O
?
-
degradation
-
-
?
amyloid beta-peptide + H2O
?
-
degradation, amyloid beta-peptide is the key component of Alzheimer disease-associated senile plaques, genetic linkage and association of Alzheimer disease on chromosome 10q23-24 in the region harboring the IDE gene, chromosome 10-linked Alzheimer disease families show decreased enzyme activity, overview
-
-
?
amyloid beta-peptide + H2O
?
degradation, IDE has no effect on the secreted ectodomain of the amyloid precursor protein derivative generated by alpha-secretase
-
-
?
amyloid beta-peptide + H2O
?
-
degradation, role for insulysin in regulating amyloid beta peptide levels in the brain
-
-
?
amyloid beta-peptide + H2O
?
-
activation in trans is observed with extended substrates that occupy both the active and distal sites
-
-
?
amyloid beta-peptide + H2O
?
-
-
-
?
amyloid beta-peptide + H2O
?
-
degradation
-
-
?
amyloid beta-peptide + H2O
?
-
degradation, role for insulysin in regulating amyloid beta peptide levels in the brain
-
-
?
amyloid beta-peptide + H2O
?
-
IDE is involved in clearance of amyloid-beta pepetide in the brain, enzyme deficiency may participate in the progression of Alzheimer's disease
-
-
?
amyloid beta-peptide + H2O
?
-
degradation
-
-
?
amyloid beta-peptide + H2O
?
-
degradation, role for insulysin in regulating amyloid beta peptide levels in the brain
-
-
?
amyloid beta-peptide 1-40 + H2O
?
-
cleavage occurs at peptide bonds Phe19-Phe20, Phe20-Ala21, and Leu34-Met35, with the latter cleavage site being the initial and principal one
-
?
amyloid beta-peptide 1-40 + H2O
?
-
-
-
-
?
amyloid beta-peptide 1-40 + H2O
?
-
76 kDa and 56 kDa fragments of IDE, derived from cleavage with proteinase K, exhibit a low level of catalytic activity but retain the ability to bind the substrate with a similar affinity as the full-length enzyme, and they retain the regulatory cationic binding site that binds ATP
-
-
?
amyloid beta-protein + H2O
?
-
-
-
?
amyloid beta-protein + H2O
?
-
-
-
-
?
amyloid beta-protein + H2O
?
-
-
-
?
amyloid beta-protein + H2O
?
-
-
-
-
?
amyloid beta40 + H2O
amyloid beta40 peptide fragments
Abeta40, an Alzheimer amyloid beta peptide
-
-
?
amyloid beta40 + H2O
amyloid beta40 peptide fragments
an Alzheimer amyloid beta peptide
-
-
?
amyloid beta40 + H2O
amyloid beta40 peptide fragments
-
-
-
-
?
amyloid beta42 + H2O
amyloid beta42 peptide fragments
Abeta42, an Alzheimer amyloid beta peptide
-
-
?
amyloid beta42 + H2O
amyloid beta42 peptide fragments
an Alzheimer amyloid beta peptide
-
-
?
amyloid-beta + H2O
?
activity is driven by the dynamic equilibrium between Abeta monomers and higher ordered aggregates. Met35-Val36 is a cleavage site in the amyloid-beta sequence. Amyloid-beta fragments resulting from cleavage by insulin-degrading enzyme form non-toxic amorphous aggregates
-
-
?
amyloid-beta + H2O
?
amyloid-beta monomers, either alone in solution or in dynamic equilibrium with higher aggregates, are cleaved at multiple sites by activity of insulin-degrading enzyme. Met35-Val36 is a cleavage site in the amyloid-beta sequence. Amyloid-beta fragments resulting from cleavage by insulin-degrading enzyme form non-toxic amorphous aggregates
-
-
?
amyloid-beta peptide + H2O
?
-
-
?
amyloid-beta peptide + H2O
?
-
-
-
?
ATP + H2O
ADP + phosphate
-
insulin-binding and degradation are dependent on ATP concentration, however, insulin does not modify the ATPase activity of IDE
-
-
?
ATP + H2O
ADP + phosphate
-
the enzyme contains one ATP binding site per enzyme molecule
-
-
?
Atrial natriuretic factor + H2O
?
-
-
-
-
?
Atrial natriuretic factor + H2O
?
-
-
-
-
?
Atrial natriuretic factor + H2O
?
-
-
-
-
?
Atrial natriuretic factor + H2O
?
-
-
-
-
?
beta-amyloid protein + H2O
?
-
-
-
?
beta-amyloid protein + H2O
?
-
-
-
?
beta-endorphin + H2O
?
-
-
-
?
beta-endorphin + H2O
?
-
-
-
?
beta-endorphin + H2O
?
-
-
-
-
?
beta-endorphin + H2O
?
-
-
-
?
beta-endorphin + H2O
?
-
76 kDa and 56 kDa fragments of IDE, derived from cleavage with proteinase K, exhibit a low level of catalytic activity but retain the ability to bind the substrate with a similar affinity as the full-length enzyme, and they retain the regulatory cationic binding site that binds ATP
-
-
?
beta-endorphin + H2O
gamma-endorphin + ?
-
-
-
-
?
beta-endorphin + H2O
gamma-endorphin + ?
-
-
?
beta-endorphin + H2O
gamma-endorphin + ?
-
-
-
?
beta-endorphin + H2O
gamma-endorphin + ?
-
-
-
-
?
bradykinin + H2O
?
-
-
-
?
bradykinin + H2O
?
-
cleavage at Pro/Phe site
-
-
?
bradykinin + H2O
?
-
-
-
?
bradykinin + H2O
?
-
-
-
?
Glucagon + H2O
?
-
-
-
?
Glucagon + H2O
?
-
-
-
-
?
Glucagon + H2O
?
-
degradation
-
-
?
Glucagon + H2O
?
the enzyme modulates blood glucose levels by cleaving insulin, a hormone that promotes glucose clearance. It also degrades glucagon, a hormone that elevates glucose levels and opposes the effect of insulin
-
-
?
Glucagon + H2O
?
-
-
-
-
?
Glucagon + H2O
Hydrolyzed glucagon
-
-
-
-
?
Glucagon + H2O
Hydrolyzed glucagon
-
-
-
-
?
Glucagon + H2O
Hydrolyzed glucagon
-
-
-
-
?
Glucagon + H2O
Hydrolyzed glucagon
-
-
-
-
?
Glucagon + H2O
Hydrolyzed glucagon
-
-
appearance of: tyrosine, leucine, lysine, alanine and phenylalanine
?
Glucagon + H2O
Hydrolyzed glucagon
-
-
-
-
?
InsL3 + H2O
InsL3 fragments
-
-
-
-
?
InsL3 + H2O
InsL3 fragments
-
human substrate, degradation
-
-
?
insulin + H2O
?
-
-
-
?
insulin + H2O
?
-
insulin degrading enzyme is unlikely to be the relevant enzyme for endosomal proteolysis of internalized insulin in liver parenchyma
-
-
?
insulin + H2O
?
-
implicated in the process of membrane fusion and cell development
-
-
?
insulin + H2O
?
-
insulin degradation
-
-
?
insulin + H2O
?
-
the enzyme may play a general role in hormone metabolism and cellular regulation
-
-
?
insulin + H2O
?
-
important role in the metabolism of insulin
-
-
?
insulin + H2O
?
-
-
-
-
?
insulin + H2O
?
-
-
-
-
?
insulin + H2O
?
-
-
-
-
?
insulin + H2O
?
-
degradation
-
-
?
insulin + H2O
?
-
insulin degrading enzyme is unlikely to be the relevant enzyme for endosomal proteolysis of internalized insulin in liver parenchyma
-
-
?
insulin + H2O
?
-
implicated in the process of membrane fusion and cell development
-
-
?
insulin + H2O
?
-
insulin degradation
-
-
?
insulin + H2O
?
-
the enzyme may play a general role in hormone metabolism and cellular regulation
-
-
?
insulin + H2O
?
-
degradation, insulin internalized into Hep-G2 cells is able cross-link with intracellular insulysin
-
-
?
insulin + H2O
?
-
degradation, insulin occurs only in grade 3 tumors, whereas grade 2 carcinomas and the normal mammary gland are each insulin-negative, overview
-
-
?
insulin + H2O
?
-
degradation, reduced insulin degradation leads to type 2 diabetes, regulation, overview
-
-
?
insulin + H2O
?
-
degradation, tissue-specific regulation, overview
-
-
?
insulin + H2O
?
-
IDE is involved in the cellular insulin metabolism, insulin inhibits protein degradation via an interaction with IDE, regulation of protein degradation by insulin-degrading enzyme, overview
-
-
?
insulin + H2O
?
-
bovine substrate, degradation, identification of clevage sites in the alpha- and beta-chains, and of the produced proteolytic fragments by AP/MALDI-mass spectrometry, method evaluation, overview
-
-
?
insulin + H2O
?
in HEK cells the enzyme has little impact on insulin clearance
-
-
?
insulin + H2O
?
the enzyme modulates blood glucose levels by cleaving insulin, a hormone that promotes glucose clearance. It also degrades glucagon, a hormone that elevates glucose levels and opposes the effect of insulin
-
-
?
insulin + H2O
?
-
implicated in the process of membrane fusion and cell development
-
-
?
insulin + H2O
?
-
insulin degradation
-
-
?
insulin + H2O
?
-
the enzyme may play a general role in hormone metabolism and cellular regulation
-
-
?
insulin + H2O
?
-
-
-
-
?
insulin + H2O
?
-
-
-
-
?
insulin + H2O
?
-
degradation
-
-
?
insulin + H2O
?
-
degradation, insulin internalized into Hep-G2 cells is able cross-link with intracellular insulysin
-
-
?
insulin + H2O
?
-
degradation, reduced insulin degradation leads to type 2 diabetes, regulation, overview
-
-
?
insulin + H2O
?
the enzyme is implicated in proteolysis of insulin
-
-
?
insulin + H2O
?
the enzyme plays a critical role in both the proteolytic degradation and inactivation of insulin
-
-
?
insulin + H2O
?
-
-
-
-
?
insulin + H2O
?
-
degradation
-
-
?
insulin + H2O
?
-
physiolgical substrate
-
?
insulin + H2O
?
-
insulin degrading enzyme is unlikely to be the relevant enzyme for endosomal proteolysis of internalized insulin in liver parenchyma
-
-
?
insulin + H2O
?
-
stepwise degradation occurs in vivo, an early step in the process is the cleavage of the B-chain between Tyr16 and Leu17, that renders the molecule susceptible to further degradation by nonspecific proteases
-
-
?
insulin + H2O
?
-
seems to be implicated in insulin metabolism to terminate the response of cells to hormone, as well as in other biological functions, including muscle differentiation, regulation of growth factor levels and antigen processing
-
-
?
insulin + H2O
?
-
implicated in the process of membrane fusion and cell development
-
-
?
insulin + H2O
?
-
major route of insulin catabolism in body
-
-
?
insulin + H2O
?
-
insulin degradation
-
-
?
insulin + H2O
?
-
the enzyme may play a general role in hormone metabolism and cellular regulation
-
-
?
insulin + H2O
?
-
degradation, insulin-binding and degradation are dependent on ATP concentration, however, insulin does not modify the ATPase activity of IDE
-
-
?
insulin + H2O
?
-
degradation, reduced insulin degradation leads to type 2 diabetes, regulation, overview
-
-
?
insulin + H2O
?
-
degradation, type 2 diabetic GK rats exhibit defects in both insulin action and insulin degradation mainly due to mutation H18R and A890V in the insulysin protein
-
-
?
insulin + H2O
?
-
76 kDa and 56 kDa fragments of IDE, derived from cleavage with proteinase K, exhibit a low level of catalytic activity but retain the ability to bind the substrate with a similar affinity as the full-length enzyme, and they retain the regulatory cationic binding site that binds ATP
-
-
?
insulin + H2O
?
-
porcine substrate, degradation
-
-
?
insulin + H2O
?
-
investigation of activity of IDE regarding cleavage site's preferentiality upon modification of environmental factors by atmospheric pressure/laser desorption ionization-mass spectrometry. The first insulin fragments produced by IDE are mainly [A (1-13) + B (1-9)], [A (1-14) + B (1-9)] and [A (1-14) + B (1-10)]. A second set of insulin fragments involving the C-terminal residues of the insulin A chain [A (14-21) and A (15-21)] and the fragments B (17-24) and B (17-25) are then produced, confirming a delayed action of IDE on these cleavage sites. A third set of insulin fragments at lower and higher m/z values start to appear soon after and their intensity increases as the intensity of the middle fragments intensity decreases
-
-
?
Insulin + H2O
Hydrolyzed insulin
-
-
-
-
?
Insulin + H2O
Hydrolyzed insulin
-
-
-
-
?
Insulin + H2O
Hydrolyzed insulin
-
-
-
-
?
Insulin + H2O
Hydrolyzed insulin
-
not: individual A and B-chains of insulin
-
-
?
Insulin + H2O
Hydrolyzed insulin
-
Drosophila and rat enzyme cleave the A-chain of intact insulin between residues A13-A14 and A14-A15
-
?
Insulin + H2O
Hydrolyzed insulin
-
the Drosophila enzyme cleaves the B-chain of intact insulin at B10-B11, B14-B15, B16-B17 and B25-B26
-
?
Insulin + H2O
Hydrolyzed insulin
-
equine
-
-
?
Insulin + H2O
Hydrolyzed insulin
Frog
-
-
-
-
?
Insulin + H2O
Hydrolyzed insulin
-
-
-
-
?
Insulin + H2O
Hydrolyzed insulin
-
much better degradation than insulin growth factor II
-
-
?
Insulin + H2O
Hydrolyzed insulin
-
specific for insulin
degradation products are smaller than the A-chain of insulin
?
Insulin + H2O
Hydrolyzed insulin
-
-
-
-
?
Insulin + H2O
Hydrolyzed insulin
-
-
-
-
?
Insulin + H2O
Hydrolyzed insulin
-
-
31312, 31313, 31315, 31317, 31318, 31320, 31321, 31322, 31323, 31324, 31325, 31326, 31327, 31328, 31330, 31331, 31333, 31337, 31339, 31340 -
-
?
Insulin + H2O
Hydrolyzed insulin
-
bovine
-
-
?
Insulin + H2O
Hydrolyzed insulin
-
porcine
-
?
Insulin + H2O
Hydrolyzed insulin
-
Drosophila and rat enzyme cleave the A-chain of intact insulin between residues A13-A14 and A14-A15
-
?
Insulin + H2O
Hydrolyzed insulin
-
degradation of 4 monoiodoinsulin isomers
-
?
Insulin + H2O
Hydrolyzed insulin
-
specific for insulin
stepwise degradation occurs in vivo, an early step in the process is the cleavage of the B-chain at Tyr16-Leu17
?
Insulin + H2O
Hydrolyzed insulin
-
the insulin protease appears to first degrade insulin to multiple products with molecular sizes slightly smaller than insulin and subsequently to small peptides (e.g. containing tyrosine A-19) and amino acids (e.g. tyrosine A-14, B-16 and B-26)
-
?
Insulin + H2O
Hydrolyzed insulin
-
-
-
-
?
Insulin + H2O
Hydrolyzed insulin
-
not: individual A and B-chains of insulin
-
-
?
insulin + H2O
insulin fragments
-
-
-
-
?
insulin + H2O
insulin fragments
-
degradation
-
-
?
insulin + H2O
insulin peptide fragments
-
-
-
-
?
insulin + H2O
insulin peptide fragments
-
high specificity
-
-
?
insulin + H2O
insulin peptide fragments
-
rapid degradation into inactive peptide fragments
-
-
?
insulin + H2O
insulin peptide fragments
-
IDE forms an enclosed catalytic chamber that completely engulfs and intimately interacts with a partially unfolded insulin molecule. The unique size, shape, charge distribution, and exosite of the IDE catalytic chamber contribute to its high affinity for insulin, IDE-insulin binding structure and interaction analysis, overview
-
-
?
insulin + H2O
insulin peptide fragments
-
IDE uses the size and charge distribution of the catalytic chamber and structural flexibility of the substrates to selectively recognize and degrade insulin
-
-
?
insulin + H2O
insulin peptide fragments
-
-
-
-
?
insulin + H2O
insulin peptide fragments
-
IDE uses the size and charge distribution of the catalytic chamber and structural flexibility of the substrates to selectively recognize and degrade insulin
-
-
?
insulin + H2O
insulin peptide fragments
-
-
-
-
?
insulin + H2O
insulin peptide fragments
-
high specificity
-
-
?
insulin + H2O
insulin peptide fragments
-
cleavage of the B-chain
-
-
?
insulin + H2O
insulin peptide fragments
-
IDE uses the size and charge distribution of the catalytic chamber and structural flexibility of the substrates to selectively recognize and degrade insulin
-
-
?
insulin + H2O
insulin peptide fragments
-
-
-
-
?
Insulin B-chain + H2O
?
-
-
-
-
?
Insulin B-chain + H2O
?
-
-
-
?
Insulin growth factor II + H2O
?
-
-
-
-
?
Insulin growth factor II + H2O
?
-
-
-
-
?
insulin-like growth factor I + H2O
insulin-like growth factor I peptide fragments
-
-
-
-
?
insulin-like growth factor I + H2O
insulin-like growth factor I peptide fragments
-
-
-
-
?
insulin-like growth factor II + H2O
insulin-like growth factor II peptide fragments
-
-
-
-
?
insulin-like growth factor II + H2O
insulin-like growth factor II peptide fragments
-
-
-
-
?
insulin-like peptide 3 + H2O
processed insulin-like peptide 3 + WSTEA
-
IDE cleaves the peptide bond between R26 and W27 of the B-chain, and releases a pentapeptide, WSTEA, from the C-terminal of the B-chain
-
-
?
insulin-like peptide 3 + H2O
processed insulin-like peptide 3 + WSTEA
-
IDE cleaves the peptide bond between R26 and W27 of the B-chain, and releases a pentapeptide, WSTEA, from the C-terminal of the B-chain, cleavage product identification by mass spectrometry, INSL-3 structure, overview
-
-
?
islet amyloid polypeptide + H2O
?
degradation of islet amyloid polypeptide in beta-cells
-
-
?
islet amyloid polypeptide + H2O
?
degradation of monomeric, but not oligomeric islet amyloid polypeptide in vitro
-
-
?
Oxidatively damaged hemoglobin + H2O
?
-
-
-
-
?
Oxidatively damaged hemoglobin + H2O
?
-
-
-
-
?
Oxidatively damaged hemoglobin + H2O
?
-
-
-
-
?
Oxidatively damaged hemoglobin + H2O
?
-
-
-
-
?
peptide V + H2O
?
-
a bradykinin-mimetic fluorogenic peptide substrate V
-
-
?
peptide V + H2O
?
-
a bradykinin-mimetic fluorogenic peptide substrate V
-
-
?
peptide V + H2O
?
-
a bradykinin-mimetic fluorogenic peptide substrate V
-
-
?
relaxin + H2O
relaxin fragments
-
-
-
-
?
relaxin + H2O
relaxin fragments
-
procine substrate, degradation
-
-
?
relaxin-3 + H2O
relaxin-3 fragments
-
-
-
-
?
relaxin-3 + H2O
relaxin-3 fragments
-
human substrate, degradation
-
-
?
somatostatin + H2O
?
-
cleavage at Phe6-Phe7 bond
-
-
?
somatostatin + H2O
?
somatostatin in addition to being a substrate, is also able to bind to two additional exosites, which play different roles according to the size of the substrate and its binding mode to the catalytic cleft of the enzyme. One exosite, which displays high affinity for somatostatin, regulates only the interaction of insulin-degrading-enzyme with larger substrates (such as insulin and beta-amyloid1-40) in a differing fashion according to their various modes of binding to the enzyme. A second exosite, which is involved in the regulation of enzymatic processing by the enzyme of all substrates investigated (including a 10-25 amino acid long amyloid-like peptide, bradykinin and somatostatin itself), probably acts through the alteration of an open-closed equilibrium
-
-
?
Transforming growth factor + H2O
?
-
-
-
-
?
Transforming growth factor + H2O
?
-
-
-
-
?
Transforming growth factor + H2O
?
-
-
-
-
?
Transforming growth factor + H2O
?
-
-
-
-
?
[(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH + H2O
[(7-methoxycoumarin-4-yl)acetyl]-RPPGF + SAFK(Dnp)-OH
-
-
-
ir
[(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH + H2O
[(7-methoxycoumarin-4-yl)acetyl]-RPPGF + SAFK(Dnp)-OH
-
-
-
ir
additional information
?
-
-
insulin-like growth factor I
-
-
?
additional information
?
-
-
fructose 1,6-bisphosphatase
-
-
?
additional information
?
-
-
hexosephosphate isomerase
-
-
?
additional information
?
-
-
aldolase
-
-
?
additional information
?
-
-
the conserved glutamate in the zinc-binding site of human enzyme is a major catalytic residue, while a conserved cysteine in this region is not essential for catalysis
-
-
?
additional information
?
-
-
no inactivation of: lactate dehydrogenase
-
-
?
additional information
?
-
-
thyroid-stimulating hormone
-
-
?
additional information
?
-
-
prolactin
-
-
?
additional information
?
-
-
hexokinase
-
-
?
additional information
?
-
-
not: growth hormone
-
-
?
additional information
?
-
-
does not act on glucagon-like peptide 1, nerve growth factor, somatostatin, bradykinin, vasopressin, platelet-derived growth factor, and vasoactive intestinal peptide, proinsulin, epidermal growth factor and IGF-I bind to the enzyme but are not efficiently degraded
-
?
additional information
?
-
-
enzyme can degrade cleaved mitochondrial targeting sequences, role of enzyme within mitochondria
-
-
?
additional information
?
-
-
hyperinsulinemia is probably elevated through insulin's competitition with amyloid beta-peptide for the enzyme, IDE deficiency might be involved in development of Alzheimer's disease, regulation, overview
-
-
?
additional information
?
-
-
membrane-bound, but not cytosolic, enzyme selectively decreases during hippocampal development from mild cognitive impairment to mild to severe Alzheimer's disease, overview
-
-
?
additional information
?
-
-
no association of IDE haplotypes with the risk of dementia, IDE may be indirectly related to dementia via its regulation of insulin levels, but it is not a major gene for Alzheimers disease
-
-
?
additional information
?
-
-
regulation of enzyme expression in the liver, overview
-
-
?
additional information
?
-
-
the human enzyme interacts with Varicella-zoster virus glycoprotein E, gE, facilitating viral infection and cell-to-cell spread of the virus, and thus serving as a cellular receptor for the virus, the binding region of the viral protein is located at amino acids 32 to 71 of gE, deletion of this sequence leads to loss of binding ability, overview, the secondary structure of the IDE binding domain is likely important for its interaction with IDE
-
-
?
additional information
?
-
-
the insulin-degrading enzyme is genetically associated with Alzheimer's disease in the Finnish population, overview
-
-
?
additional information
?
-
-
IDE has a preference for basic or hydrophobic amino acids at the carboxyl side of cleavage sites, overview, the catalytic domain of IDE is located in the amino subunit
-
-
?
additional information
?
-
-
the enzyme is a neutral thiol metalloprotease with the active site sequence HEXXH
-
-
?
additional information
?
-
-
IDE is a neutral thiol metalloprotease
-
-
?
additional information
?
-
-
IDE is involved in the clearance of many bioactive peptide substrates, including insulin and amyloid beta, peptides vital to the development of diabetes and Alzheimer's disease, respectively. IDE can also rapidly degrade hormones that are held together by intramolecular disulfide bond(s) without their reduction. Furthermore, IDE exhibits a remarkable ability to preferentially degrade structurally similar peptides such as the selective degradation of insulin-like growth factor-II and transforming growth factor-alpha, TGF-alpha, over IGF-I and epidermal growth factor, respectively. IDE cleaves its substrates at multiple sites in a biased stochastic manner
-
-
?
additional information
?
-
active site structure of IDE, overview. Interactions of the two full-length Alzheimer amyloid beta peptides, Abeta40 and Abeta42, with the fully active form of IDE through unrestrained, all-atom molecular dynamics simulations, using free and small fragment-bound, Asp1-Glu3 and Lys16-Asp23 of Abeta40 and Asp1-Glu3 and Lys16-Glu22 of Abeta42, mutated forms of IDE and NMR structures of the full-length Abeta40 and Abeta42, overview. In comparison to Abeta40, Abeta42 is more flexible and interacts through a smaller number, 17-22, of hydrogen bonds in the catalytic chamber of IDE. Both the substrates adopt more beta-sheet character in the IDE environment. Hydrogen bonding interactions between IDE and substrates amyloidbeta40 and amyloidbeta42, overview
-
-
?
additional information
?
-
-
IDE shows catalytic activity toward two peptides of different length, simulating a portion of B chain of insulin, analysis by density functional theory method and the hybrid exchange-correlation functional B3LYP in gas phase and in the protein environment, modelling, reaction mechanism, overview. The proteolysis reaction is exothermic and proceeds quickly as the barrier in the rate-limiting step falls widely within the range of values expected for an enzymatic catalysis
-
-
?
additional information
?
-
-
the putative ATP-binding domain is a key modulator of IDE proteolytic activity
-
-
?
additional information
?
-
-
the substrates often possess disulfide bonds that are involved in enzyme-substrate interactions, e.g. insulin possesses three disulfide bonds. The exosite interaction serves as a molecular tether allowing the proper positioning of the C-terminal end of the substrate to the catalytic site, exosite binding ligands can activate the enzyme, the exosite has regulatory function. Tyr831 is also involved in substrate positioning, enzyme-substrate interactions required for the regulation of the enzyme with open and closed stages, mechanism, overview. The closed stage in absence of substrate is unstable. IDE is an allosteric enzyme
-
-
?
additional information
?
-
the enzyme selectively degrades biologically important substrates associated with type 2 diabetes and Alzheimer's disease
-
-
?
additional information
?
-
a functional requirement for active site residues F115, A140, F141, Y150, W199, F202, F820, and Y831 is established, and specific contributions of residue charge, size, and hydrophobicity to substrate binding, specificity, and proteolysis are demonstrated
-
-
?
additional information
?
-
-
a functional requirement for active site residues F115, A140, F141, Y150, W199, F202, F820, and Y831 is established, and specific contributions of residue charge, size, and hydrophobicity to substrate binding, specificity, and proteolysis are demonstrated
-
-
?
additional information
?
-
-
hyperinsulinemia is probably elevated through insulin's competition with amyloid beta-peptide for the enzyme, IDE deficiency might be involved in development of Alzheimer's disease, regulation, overview
-
-
?
additional information
?
-
-
the enzyme is a neutral thiol metalloprotease with the active site sequence HEXXH
-
-
?
additional information
?
-
-
the substrates often possess disulfide bonds that are involved in enzyme-substrate interactions, e.g. insulin possesses three disulfide bonds. The exosite interaction serves as a molecular tether allowing the proper positioning of the C-terminal end of the substrate to the catalytic site, exosite binding ligands can activate the enzyme, the exosite has regulatory function. IDE is an allosteric enzyme
-
-
?
additional information
?
-
-
-
-
-
?
additional information
?
-
-
-
-
-
?
additional information
?
-
-
requirement for optimal substrate activity is the deblocking of the amino end of the A-chain
-
-
?
additional information
?
-
-
human growth hormone is not appreciably degraded
-
-
?
additional information
?
-
-
EGF and insulin C-peptide are no substrates
-
?
additional information
?
-
-
gamma-endorphin, Leu-Arg, and Leu-enkephalin are not significantly cleaved
-
?
additional information
?
-
-
enzyme may participate in prostatic and uterine growth
-
-
?
additional information
?
-
-
hyperinsulinemia is probably elevated through insulin's competition with amyloid beta-peptide for the enzyme, IDE deficiency might be involved in development of Alzheimer's disease, regulation, overview
-
-
?
additional information
?
-
-
the enzyme is a neutral thiol metalloprotease with the active site sequence HEXXH
-
-
?
additional information
?
-
-
IDE interacts with vimentin and with nestin during mitosis, vimentin binds IDE with a higher affinity than nestin in vitro. The interaction between vimentin and IDE is enhanced by vimentin phosphorylation at Ser55, the interaction between nestin and IDE is phosphorylation-independent. Nestin-mediated disassembly of vimentin IFs generates a structure capable of sequestering and modulating the activity of IDE, overview
-
-
?
additional information
?
-
-
the substrates often possess disulfide bonds that are involved in enzyme-substrate interactions, e.g. insulin possesses three disulfide bonds. The exosite interaction serves as a molecular tether allowing the proper positioning of the C-terminal end of the substrate to the catalytic site, exosite binding ligands can activate the enzyme, the exosite has regulatory function. Regulatory mechanism, overview. IDE is an allosteric enzyme
-
-
?
additional information
?
-
-
preference for small substrates 2000-6000 MW
-
-
?
additional information
?
-
-
IDE interacts with vimentin and nestin, vimentin binds IDE with a higher affinity than nestin in vitro. A nestin tail fragment interacts with insulin-degrading enzyme in Xenopus egg extracts, overview. The interaction between vimentin and IDE is enhanced by vimentin phosphorylation at Ser55, the interaction between nestin and IDE is phosphorylation-independent. Nestin-mediated disassembly of vimentin IFs generates a structure capable of sequestering and modulating the activity of IDE, overview
-
-
?
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amylin + H2O
amylin peptide fragments
amyloid alpha-peptide + H2O
?
-
-
-
?
amyloid beta + H2O
?
role of insulin-degrading enzyme in the intracytosolic clearance of amyloid beta and other amyloid-like peptides
-
-
?
amyloid beta + H2O
amyloid beta peptide fragments
amyloid beta peptide 1-40 + H2O
?
-
physiolgical substrate
-
?
amyloid beta-peptide + H2O
?
amyloid beta-peptide 1-40 + H2O
?
-
-
-
-
?
amyloid beta40 + H2O
amyloid beta40 peptide fragments
amyloid beta42 + H2O
amyloid beta42 peptide fragments
Abeta42, an Alzheimer amyloid beta peptide
-
-
?
amyloid-beta + H2O
?
activity is driven by the dynamic equilibrium between Abeta monomers and higher ordered aggregates. Met35-Val36 is a cleavage site in the amyloid-beta sequence. Amyloid-beta fragments resulting from cleavage by insulin-degrading enzyme form non-toxic amorphous aggregates
-
-
?
ATP + H2O
ADP + phosphate
-
insulin-binding and degradation are dependent on ATP concentration, however, insulin does not modify the ATPase activity of IDE
-
-
?
beta-endorphin + H2O
?
-
-
-
-
?
beta-endorphin + H2O
gamma-endorphin + ?
epidermal growth factor + H2O
epidermal growth factor peptide fragments
-
identification of cleavage sites by mass spectrometry and NMR
-
-
?
glucagon + H2O
glucagon peptide fragments
-
-
-
-
?
InsL3 + H2O
InsL3 fragments
-
-
-
-
?
insulin + H2O
insulin fragments
-
-
-
-
?
insulin + H2O
insulin peptide fragments
insulin-like growth factor I + H2O
insulin-like growth factor I peptide fragments
insulin-like growth factor II + H2O
insulin-like growth factor II peptide fragments
insulin-like growth factor-II + H2O
insulin-like growth factor-II peptide fragments
-
identification of cleavage sites by mass spectrometry and NMR
-
-
?
insulin-like peptide 3 + H2O
processed insulin-like peptide 3 + WSTEA
-
IDE cleaves the peptide bond between R26 and W27 of the B-chain, and releases a pentapeptide, WSTEA, from the C-terminal of the B-chain
-
-
?
islet amyloid polypeptide + H2O
?
degradation of islet amyloid polypeptide in beta-cells
-
-
?
reduced amylin + H2O
reduced amylin peptide fragments
-
identification of cleavage sites by mass spectrometry
-
-
?
relaxin + H2O
relaxin fragments
-
-
-
-
?
relaxin-3 + H2O
relaxin-3 fragments
-
-
-
-
?
transforming growth factor-alpha + H2O
transforming growth factor-alpha peptide fragments
-
identification of cleavage sites by mass spectrometry
-
-
?
additional information
?
-
amylin + H2O
?
-
degradation
-
-
?
amylin + H2O
?
-
degradation
-
-
?
amylin + H2O
?
-
degradation
-
-
?
amylin + H2O
amylin peptide fragments
-
-
-
-
?
amylin + H2O
amylin peptide fragments
-
identification of cleavage sites by mass spectrometry and NMR. The presence of a disulfide bond in amylin allows IDE to cut at an additional site in the middle of the peptide, amino acids 18-19, binding structure, overview
-
-
?
amyloid beta + H2O
amyloid beta peptide fragments
-
-
-
-
?
amyloid beta + H2O
amyloid beta peptide fragments
-
-
-
-
?
amyloid beta-peptide + H2O
?
-
-
-
?
amyloid beta-peptide + H2O
?
-
-
-
-
?
amyloid beta-peptide + H2O
?
-
degradation
-
-
?
amyloid beta-peptide + H2O
?
-
degradation, amyloid beta-peptide is the key component of Alzheimer disease-associated senile plaques, genetic linkage and association of Alzheimer disease on chromosome 10q23-24 in the region harboring the IDE gene, chromosome 10-linked Alzheimer disease families show decreased enzyme activity, overview
-
-
?
amyloid beta-peptide + H2O
?
degradation, IDE has no effect on the secreted ectodomain of the amyloid precursor protein derivative generated by alpha-secretase
-
-
?
amyloid beta-peptide + H2O
?
-
degradation, role for insulysin in regulating amyloid beta peptide levels in the brain
-
-
?
amyloid beta-peptide + H2O
?
-
degradation
-
-
?
amyloid beta-peptide + H2O
?
-
degradation, role for insulysin in regulating amyloid beta peptide levels in the brain
-
-
?
amyloid beta-peptide + H2O
?
-
IDE is involved in clearance of amyloid-beta pepetide in the brain, enzyme deficiency may participate in the progression of Alzheimer's disease
-
-
?
amyloid beta-peptide + H2O
?
-
degradation
-
-
?
amyloid beta-peptide + H2O
?
-
degradation, role for insulysin in regulating amyloid beta peptide levels in the brain
-
-
?
amyloid beta40 + H2O
amyloid beta40 peptide fragments
Abeta40, an Alzheimer amyloid beta peptide
-
-
?
amyloid beta40 + H2O
amyloid beta40 peptide fragments
-
-
-
-
?
beta-endorphin + H2O
gamma-endorphin + ?
-
-
-
-
?
beta-endorphin + H2O
gamma-endorphin + ?
-
-
-
-
?
Glucagon + H2O
?
-
-
-
-
?
Glucagon + H2O
?
-
degradation
-
-
?
Glucagon + H2O
?
the enzyme modulates blood glucose levels by cleaving insulin, a hormone that promotes glucose clearance. It also degrades glucagon, a hormone that elevates glucose levels and opposes the effect of insulin
-
-
?
Glucagon + H2O
?
-
-
-
-
?
insulin + H2O
?
-
insulin degrading enzyme is unlikely to be the relevant enzyme for endosomal proteolysis of internalized insulin in liver parenchyma
-
-
?
insulin + H2O
?
-
implicated in the process of membrane fusion and cell development
-
-
?
insulin + H2O
?
-
insulin degradation
-
-
?
insulin + H2O
?
-
the enzyme may play a general role in hormone metabolism and cellular regulation
-
-
?
insulin + H2O
?
-
important role in the metabolism of insulin
-
-
?
insulin + H2O
?
-
-
-
-
?
insulin + H2O
?
-
-
-
-
?
insulin + H2O
?
-
degradation
-
-
?
insulin + H2O
?
-
insulin degrading enzyme is unlikely to be the relevant enzyme for endosomal proteolysis of internalized insulin in liver parenchyma
-
-
?
insulin + H2O
?
-
implicated in the process of membrane fusion and cell development
-
-
?
insulin + H2O
?
-
insulin degradation
-
-
?
insulin + H2O
?
-
the enzyme may play a general role in hormone metabolism and cellular regulation
-
-
?
insulin + H2O
?
-
degradation, insulin internalized into Hep-G2 cells is able cross-link with intracellular insulysin
-
-
?
insulin + H2O
?
-
degradation, insulin occurs only in grade 3 tumors, whereas grade 2 carcinomas and the normal mammary gland are each insulin-negative, overview
-
-
?
insulin + H2O
?
-
degradation, reduced insulin degradation leads to type 2 diabetes, regulation, overview
-
-
?
insulin + H2O
?
-
degradation, tissue-specific regulation, overview
-
-
?
insulin + H2O
?
-
IDE is involved in the cellular insulin metabolism, insulin inhibits protein degradation via an interaction with IDE, regulation of protein degradation by insulin-degrading enzyme, overview
-
-
?
insulin + H2O
?
in HEK cells the enzyme has little impact on insulin clearance
-
-
?
insulin + H2O
?
the enzyme modulates blood glucose levels by cleaving insulin, a hormone that promotes glucose clearance. It also degrades glucagon, a hormone that elevates glucose levels and opposes the effect of insulin
-
-
?
insulin + H2O
?
-
implicated in the process of membrane fusion and cell development
-
-
?
insulin + H2O
?
-
insulin degradation
-
-
?
insulin + H2O
?
-
the enzyme may play a general role in hormone metabolism and cellular regulation
-
-
?
insulin + H2O
?
-
-
-
-
?
insulin + H2O
?
-
degradation
-
-
?
insulin + H2O
?
-
degradation, insulin internalized into Hep-G2 cells is able cross-link with intracellular insulysin
-
-
?
insulin + H2O
?
-
degradation, reduced insulin degradation leads to type 2 diabetes, regulation, overview
-
-
?
insulin + H2O
?
the enzyme is implicated in proteolysis of insulin
-
-
?
insulin + H2O
?
the enzyme plays a critical role in both the proteolytic degradation and inactivation of insulin
-
-
?
insulin + H2O
?
-
-
-
-
?
insulin + H2O
?
-
physiolgical substrate
-
?
insulin + H2O
?
-
insulin degrading enzyme is unlikely to be the relevant enzyme for endosomal proteolysis of internalized insulin in liver parenchyma
-
-
?
insulin + H2O
?
-
stepwise degradation occurs in vivo, an early step in the process is the cleavage of the B-chain between Tyr16 and Leu17, that renders the molecule susceptible to further degradation by nonspecific proteases
-
-
?
insulin + H2O
?
-
seems to be implicated in insulin metabolism to terminate the response of cells to hormone, as well as in other biological functions, including muscle differentiation, regulation of growth factor levels and antigen processing
-
-
?
insulin + H2O
?
-
implicated in the process of membrane fusion and cell development
-
-
?
insulin + H2O
?
-
major route of insulin catabolism in body
-
-
?
insulin + H2O
?
-
insulin degradation
-
-
?
insulin + H2O
?
-
the enzyme may play a general role in hormone metabolism and cellular regulation
-
-
?
insulin + H2O
?
-
degradation, insulin-binding and degradation are dependent on ATP concentration, however, insulin does not modify the ATPase activity of IDE
-
-
?
insulin + H2O
?
-
degradation, reduced insulin degradation leads to type 2 diabetes, regulation, overview
-
-
?
insulin + H2O
?
-
degradation, type 2 diabetic GK rats exhibit defects in both insulin action and insulin degradation mainly due to mutation H18R and A890V in the insulysin protein
-
-
?
insulin + H2O
insulin peptide fragments
-
-
-
-
?
insulin + H2O
insulin peptide fragments
-
high specificity
-
-
?
insulin + H2O
insulin peptide fragments
-
rapid degradation into inactive peptide fragments
-
-
?
insulin + H2O
insulin peptide fragments
-
-
-
-
?
insulin + H2O
insulin peptide fragments
-
-
-
-
?
insulin + H2O
insulin peptide fragments
-
high specificity
-
-
?
insulin + H2O
insulin peptide fragments
-
cleavage of the B-chain
-
-
?
insulin + H2O
insulin peptide fragments
-
-
-
-
?
insulin-like growth factor I + H2O
insulin-like growth factor I peptide fragments
-
-
-
-
?
insulin-like growth factor I + H2O
insulin-like growth factor I peptide fragments
-
-
-
-
?
insulin-like growth factor II + H2O
insulin-like growth factor II peptide fragments
-
-
-
-
?
insulin-like growth factor II + H2O
insulin-like growth factor II peptide fragments
-
-
-
-
?
additional information
?
-
-
enzyme can degrade cleaved mitochondrial targeting sequences, role of enzyme within mitochondria
-
-
?
additional information
?
-
-
hyperinsulinemia is probably elevated through insulin's competitition with amyloid beta-peptide for the enzyme, IDE deficiency might be involved in development of Alzheimer's disease, regulation, overview
-
-
?
additional information
?
-
-
membrane-bound, but not cytosolic, enzyme selectively decreases during hippocampal development from mild cognitive impairment to mild to severe Alzheimer's disease, overview
-
-
?
additional information
?
-
-
no association of IDE haplotypes with the risk of dementia, IDE may be indirectly related to dementia via its regulation of insulin levels, but it is not a major gene for Alzheimers disease
-
-
?
additional information
?
-
-
regulation of enzyme expression in the liver, overview
-
-
?
additional information
?
-
-
the human enzyme interacts with Varicella-zoster virus glycoprotein E, gE, facilitating viral infection and cell-to-cell spread of the virus, and thus serving as a cellular receptor for the virus, the binding region of the viral protein is located at amino acids 32 to 71 of gE, deletion of this sequence leads to loss of binding ability, overview, the secondary structure of the IDE binding domain is likely important for its interaction with IDE
-
-
?
additional information
?
-
-
the insulin-degrading enzyme is genetically associated with Alzheimer's disease in the Finnish population, overview
-
-
?
additional information
?
-
-
IDE is a neutral thiol metalloprotease
-
-
?
additional information
?
-
-
IDE is involved in the clearance of many bioactive peptide substrates, including insulin and amyloid beta, peptides vital to the development of diabetes and Alzheimer's disease, respectively. IDE can also rapidly degrade hormones that are held together by intramolecular disulfide bond(s) without their reduction. Furthermore, IDE exhibits a remarkable ability to preferentially degrade structurally similar peptides such as the selective degradation of insulin-like growth factor-II and transforming growth factor-alpha, TGF-alpha, over IGF-I and epidermal growth factor, respectively. IDE cleaves its substrates at multiple sites in a biased stochastic manner
-
-
?
additional information
?
-
the enzyme selectively degrades biologically important substrates associated with type 2 diabetes and Alzheimer's disease
-
-
?
additional information
?
-
-
hyperinsulinemia is probably elevated through insulin's competition with amyloid beta-peptide for the enzyme, IDE deficiency might be involved in development of Alzheimer's disease, regulation, overview
-
-
?
additional information
?
-
-
enzyme may participate in prostatic and uterine growth
-
-
?
additional information
?
-
-
hyperinsulinemia is probably elevated through insulin's competition with amyloid beta-peptide for the enzyme, IDE deficiency might be involved in development of Alzheimer's disease, regulation, overview
-
-
?
additional information
?
-
-
IDE interacts with vimentin and with nestin during mitosis, vimentin binds IDE with a higher affinity than nestin in vitro. The interaction between vimentin and IDE is enhanced by vimentin phosphorylation at Ser55, the interaction between nestin and IDE is phosphorylation-independent. Nestin-mediated disassembly of vimentin IFs generates a structure capable of sequestering and modulating the activity of IDE, overview
-
-
?
additional information
?
-
-
IDE interacts with vimentin and nestin, vimentin binds IDE with a higher affinity than nestin in vitro. A nestin tail fragment interacts with insulin-degrading enzyme in Xenopus egg extracts, overview. The interaction between vimentin and IDE is enhanced by vimentin phosphorylation at Ser55, the interaction between nestin and IDE is phosphorylation-independent. Nestin-mediated disassembly of vimentin IFs generates a structure capable of sequestering and modulating the activity of IDE, overview
-
-
?
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((((S)-1-benzylcarbamoyl-2-(1H-imidazol-4-yl)-ethylcarbamoyl)-methyl)-(3-phenyl-propyl)-amino)-acetic acid
-
((((S)-2-(1H-imidazol-4-yl)-1-(3-methyl-(1,2,4)oxadiazol-5-yl)-ethylcarbamoyl)-methyl)-(3-phenyl-propyl)-amino)-acetic acid
-
((((S)-2-(1H-imidazol-4-yl)-1-(3-methyl-(1,2,4)oxadiazol-5-yl)-ethylcarbamoyl)-methyl)-(3-phenyl-propyl)-amino)-acetic acid methyl ester
less than 10% inhibition at 0.1 mM
((((S)-2-(1H-imidazol-4-yl)-1-methylcarbamoylethylcarbamoyl)-methyl)-(3-phenyl-propyl)-amino)-acetic acid
BDM43079
((((S)-2-(1H-imidazol-4-yl)-1-methylcarbamoylethylcarbamoyl)-methyl)-(3-phenyl-propyl)-amino)-acetic acid methyl ester
less than 10% inhibition at 0.1 mM
((((S)-2-hydroxy-1-(1H-imidazol-4-ylmethyl)-ethylcarbamoyl)-methyl)-(3-phenyl-propyl)-amino)-acetic acid
-
(11R,12S,13S)-13-(hydroxymethyl)-12-(2'-methylbiphenyl-4-yl)-9-[[2-(trifluoromethyl)phenyl]sulfonyl]-1,9-diazabicyclo[9.2.0]tridecan-2-one
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.00006 mM
(3R,6S,9S,12E,16S)-9-(4-aminobutyl)-3-(4-benzoylbenzyl)-6-(cyclohexylmethyl)-2,5,8,11,14-pentaoxo-1,4,7,10,15-pentaazacycloicos-12-ene-16-carboxamide
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.00005 mM
(7R,8S,9S)-8-(2',3'-dimethylbiphenyl-4-yl)-9-(hydroxymethyl)-5-[[2-(trifluoromethyl)phenyl]sulfonyl]-1,5-diazabicyclo[5.2.0]nonan-2-one
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.00012 mM
(8R,9R,10S)-N-cyclopentyl-10-(hydroxymethyl)-9-(2'-methylbiphenyl-4-yl)-1,6-diazabicyclo[6.2.0]decane-6-carboxamide
the inhibitor fully blocks insulin degradation in a concentration-dependent manner, while only weakly and partially inhibiting glucagon degradation. It inhibits wild-type enzyme, but does not inhibit A479L exo-site variant. It displays decreased affinity
(8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-10-(fluoromethyl)-6-[[2-(trifluoromethyl)phenyl]sulfonyl]-1,6-diazabicyclo[6.2.0]decane
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000024 mM
(8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-10-(hydroxymethyl)-6-[[2-(trifluoromethyl)phenyl]sulfonyl]-1,6-diazabicyclo[6.2.0]decan-2-one
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.00008 mM
(8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-10-(methoxymethyl)-6-[[2-(trifluoromethyl)phenyl]sulfonyl]-1,6-diazabicyclo[6.2.0]decane
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000075 mM
(8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-[[2-(trifluoromethyl)phenyl]sulfonyl]-1,6-diazabicyclo[6.2.0]decane-10-carboxylic acid
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.0005 mM
(9R,10S,11S)-10-(2',3'-dimethylbiphenyl-4-yl)-11-(hydroxymethyl)-7-[[2-(trifluoromethyl)phenyl]sulfonyl]-1,7-diazabicyclo[7.2.0]undecan-2-one
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.0001 mM
(benzyl-(((S)-1-benzylcarbamoyl-2-(1H-imidazol-4-yl)-ethylcarbamoyl)-methyl)-amino)-acetic acid
-
(benzyl-(((S)-1-carbamoyl-2-(1H-imidazol-4-yl)-ethylcarbamoyl)-methyl)-amino)-acetic acid
-
(benzyl-(((S)-1-dimethylcarbamoyl-2-(1H-imidazol-4-yl)-ethylcarbamoyl)-methyl)-amino)-acetic acid
-
(benzyl-(((S)-2-(1H-imidazol-4-yl)-1-methylcarbamoylethylcarbamoyl)-methyl)-amino)-acetic acid
-
(benzyl-(((S)-2-hydroxy-1-(1H-imidazol-4-ylmethyl)-ethylcarbamoyl)-methyl)-amino)-acetic acid
-
(benzyl-((2-(1H-imidazol-4-yl)-ethylcarbamoyl)-methyl)-amino)-acetic acid
less than 10% inhibition at 0.1 mM
(S)-2-(2-((4-tert-butyl-benzyl)-carboxymethyl-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
-
(S)-2-(2-(benzoyl-carboxymethyl-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
less than 10% inhibition at 0.1 mM
(S)-2-(2-(benzyl-(1H-tetrazol-5-ylmethyl)-amino)-acetylamino)-3-(1H-imidazol-4-yl)-N-methyl-propionamide
less than 10% inhibition at 0.1 mM
(S)-2-(2-(benzyl-(2-carboxy-ethyl)-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
less than 10% inhibition at 0.1 mM
(S)-2-(2-(benzyl-(2-hydroxy-3,4-dioxo-cyclobut-1-enyl)-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
-
(S)-2-(2-(benzyl-carbamoylmethyl-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
less than 10% inhibition at 0.1 mM
(S)-2-(2-(benzyl-carboxymethyl-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid
less than 10% inhibition at 0.1 mM
(S)-2-(2-(benzyl-carboxymethyl-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid isopropyl ester
-
(S)-2-(2-(benzyl-carboxymethyl-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
-
(S)-2-(2-(benzyl-carboxymethyl-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid tert-butyl ester
-
(S)-2-(2-(benzyl-carboxymethyl-amino)-acetylamino)-3-(1H-indol-3-yl)-propionic acid methyl ester
less than 10% inhibition at 0.1 mM
(S)-2-(2-(benzyl-carboxymethyl-amino)-acetylamino)-3-(3H-imidazol-4-yl)-propionic acid isobutyl ester
-
(S)-2-(2-(benzyl-carboxymethyl-amino)-acetylamino)-3-phenyl-propionic acid methyl ester
less than 10% inhibition at 0.1 mM
(S)-2-(2-(benzyl-carboxymethyl-amino)-acetylamino)-5-guanidino-pentanoic acid methyl ester
-
(S)-2-(2-(benzyl-hydroxycarbamoylmethyl-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
-
(S)-2-(2-(benzyl-methoxycarbonylmethyl-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
less than 10% inhibition at 0.1 mM
(S)-2-(2-(benzyloxycarbonyl-carboxymethyl-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
less than 10% inhibition at 0.1 mM
(S)-2-(2-(carboxymethyl-(1-methyl-3-phenyl-propyl)-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
-
(S)-2-(2-(carboxymethyl-(2-(1H-indol-3-yl)-ethyl)-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
-
(S)-2-(2-(carboxymethyl-(3-phenyl-propionyl)-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
less than 10% inhibition at 0.1 mM
(S)-2-(2-(carboxymethyl-(3-phenyl-propyl)-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
-
(S)-2-(2-(carboxymethyl-(3-phenyl-propyl)-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid tert-butyl ester
-
(S)-2-(2-(carboxymethyl-(4-fluoro-benzyl)-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
-
(S)-2-(2-(carboxymethyl-(4-methyl-benzyl)-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
-
(S)-2-(2-(carboxymethyl-(4-phenyl-butyl)-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
-
(S)-2-(2-(carboxymethyl-(4-trifluoromethyl-benzyl)-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
-
(S)-2-(2-(carboxymethyl-(n-hexyl)-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
-
(S)-2-(2-(carboxymethyl-amino)-acetylamino)-3-(1Himidazol-4-yl)-propionic acid methyl ester
less than 10% inhibition at 0.1 mM
(S)-2-(2-(carboxymethyl-methyl-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
less than 10% inhibition at 0.1 mM
(S)-2-(2-(carboxymethyl-naphthalen-2-ylmethyl-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
-
(S)-2-(2-(carboxymethyl-phenethyl-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
-
(S)-2-(2-(carboxymethyl-phenyl-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
less than 10% inhibition at 0.1 mM
(S)-2-(2-(carboxymethyl-phenylacetyl-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
less than 10% inhibition at 0.1 mM
(S)-2-(2-(carboxymethyl-pyridin-4-ylmethyl-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
-
(S)-2-(2-benzylamino-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
less than 10% inhibition at 0.1 mM
(S)-4-fluoro-N-((1-(4-(hydroxyamino)-1-(naphthalen-2-yl)-4-oxobutan-2-yl)-1H-1,2,3-triazol-4-yl)methyl)benzamide
i.e. BDM44768, catalytic site inhibitor, designed by kinetic target-guided synthesis. Selectively inhibits insulin-degrading enzyme. Crystallographic and small angle X-ray scattering analyses show that it locks insulin-degrading enzyme in a closed conformation. Acute treatment of mice with BDM44768 increases insulin signalling and impairs glucose tolerance in an insulin-degrading enzyme-dependent manner. The results casts doubt on the general usefulness of the inhibition of insulin-degrading enzyme catalytic activity to treat diabetes
1-[(8R,9R,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-[[2-(trifluoromethyl)phenyl]sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]-N,N-dimethylmethanamine
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.0001 mM
1-[(8R,9R,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-[[2-(trifluoromethyl)phenyl]sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]-N-methylmethanamine
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000007 mM
2,6-dichlorophenol-indophenol
-
uncompetitive
3-(((S)-1-methoxy-1-oxo-3-imidazol-2-yl)carbamoyl)-1,2,3,4-tetrahydroisoquinoline-2-ethanoic acid
-
3-benzyl-4-((S)-2-(1H-imidazol-4-yl)-1-methylcarbamoylethylcarbamoyl)-butyric acid
less than 10% inhibition at 0.1 mM
4'-[(8R,9S,10S)-10-(hydroxymethyl)-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-9-yl]biphenyl-3-ol
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.0073 mM
Ac-EWRFCGdPPECLYLVCG-NH2(Cys5-Cys10 disulfide)
-
Ac-EWRFCGGGdPPECLYLVCG-NH2(Cys5-Cys12-disulfide)
-
adenosine 5'-diphosphate
-
74% inhibition
adenosine 5'-O-(3thiotriphosphate)
-
36% inhibition
adrenocorticotropic hormone
-
competitive inhibition of amylin degradation
-
amylin
-
excess amylin inhibits amylin degradation, competitive inhibition
-
Aprotinin
-
22.4% inhibition
atrialnatriuretic peptide
-
competitive inhibition of amylin degradation
-
beta-gamma-methyleneadenosine 5'-triphosphate
-
65% inhibition
bradykinin
-
mixed competitive-noncompetitive
Ca2+
-
stimulates cytosolic activity, inhibits particulate activity
cholesterol
-
membranes isolated from mouse brain with endogenous reduced levels of cholesterol due to targeted deletion of one seladin-I allele show a reduced amount of IDE
diphosphate
-
46% inhibition
dynorphin B-9
-
inhibitory with insulin as substrate
EWRF-cyclo(DGdPPEDap)LYLVCG-NH2
-
EWRF-cyclo(DGGGdPPEDap)LYLVCG-NH2
-
Fragment of cytochrome c
-
-
-
glucagon
-
competitive inhibition of amylin degradation
glutathione
-
oxidized glutathione inhibits IDE through glutathionylation, which is reversible by dithiothreitol but not by ascorbic acid
guanosine 5'-triphosphate
-
38% inhibition
Inhibitor from rat liver homogenate
-
Inhibitors purified from human serum
-
-
-
InsL3
-
competitively inhibits the degradation of insulin, and crosslinking of insulin to IDE
-
insulin-like peptide 3
-
IDE degrades insulin quickly, and addition of INSL3 significantly decreases insulin degradation, competitive inhibition
-
methyl 5-[[(8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-10-(hydroxymethyl)-1,6-diazabicyclo[6.2.0]dec-6-yl]sulfonyl]-1-methyl-1H-pyrrole-2-carboxylate
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: above 0.005 mM
methyl [(2S)-2-(5-[5-[4-([(2S)-2-[(3S)-3-amino-2-oxopiperidin-1-yl]-2-cyclohexylacetyl]amino)phenyl]pentyl]-2-fluorophenyl)-3-(quinolin-3-yl)propyl]carbamate
-
methyl [(2S)-2-[4-([5-[4-([(2S)-2-[(3S)-3-amino-2-oxopiperidin-1-yl]-2-cyclohexylacetyl]amino)phenyl]pentyl]oxy)phenyl]-3-(quinolin-3-yl)butyl]carbamate
-
N-(4-[[(8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-10-(hydroxymethyl)-1,6-diazabicyclo[6.2.0]dec-6-yl]sulfonyl]-3-methylphenyl)acetamide
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.0016 mM
N-[[(2R,3S,4S)-1-acetyl-3-(2',3'-dimethylbiphenyl-4-yl)-4-(hydroxymethyl)azetidin-2-yl]methyl]-2-(trifluoromethyl)benzenesulfonamide
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000115 mM
N-[[(2R,3S,4S)-3-(2',3'-dimethylbiphenyl-4-yl)-4-(hydroxymethyl)-1-(prop-2-en-1-yl)azetidin-2-yl]methyl]-2-(trifluoromethyl)benzenesulfonamide
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.0001 mM
N-[[(2R,3S,4S)-3-(2',3'-dimethylbiphenyl-4-yl)-4-(hydroxymethyl)azetidin-2-yl]methyl]-2-(trifluoromethyl)benzenesulfonamide
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.0006 mM
N2-[(2S)-4-(hydroxyamino)-2-(naphthalen-2-ylmethyl)-4-oxobutanoyl]-L-arginyl-L-tryptophyl-L-glutamine
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.0000006 mM
Natural inhibitor of MW 67000 or 80000-120000 MW
-
reduces activity reversibly, nonprogressively, and noncompetitively with respect to insulin
-
o-phenanthroline
-
0.1 mM, wild-type, 73% residual activity, mutants H112D, H112Q, less than 2.5% residual activity
orthovanadate
-
inhibits ATP hydrolysis and insulin degradation
p-hydroxymercuribenzoate
-
-
phosphorylated vimentin
-
QSLPWCYPHCVT-NH2
the substrate contains two cysteine residues, which are predicted to form a disulfide bond that cyclizes the peptide, together with 2 proline residues. By virtue of its potency, stability, specificity for insulin-degrading enzyme, low cost of synthesis, and demonstrated ability to potentiate insulin-induced processes involved in wound healing and skin health, the inhibitor holds significant therapeutic and cosmetic potential for topical applications
Quinoline-2-thiol
-
mixed competitive-noncompetitive
relaxin
-
competitively inhibits the degradation of insulin, and crosslinking of insulin to IDE
-
relaxin-3
-
competitively inhibits the degradation of insulin, and crosslinking of insulin to IDE
-
S-nitroso-N-acetylpenicillamine
-
nitric oxide donors decrease both insulin and amyloid beta degrading activities of insulysin. Insulin-degrading activity is more sensitive to nitric oxide inhibition than amyloid beta degrading activity. Insulysin-mediated regulation of proteasome activity is affected similarly to insulin-degrading activity. S-nitrosylation of enzyme does not affect the insulin degradation products produced by the enzyme, nor does nitric oxide affect insulin binding to insulysin. Inhibition is noncompetitive
SH-group blocking reagents
-
-
-
sodium nitroprusside
-
nitric oxide donors decrease both insulin and amyloid beta degrading activities of insulysin. Insulin-degrading activity is more sensitive to nitric oxide inhibition than amyloid beta degrading activity. Insulysin-mediated regulation of proteasome activity is affected similarly to insulin-degrading activity. S-nitrosylation of enzyme does not affect the insulin degradation products produced by the enzyme, nor does nitric oxide affect insulin binding to insulysin. Inhibition is noncompetitive
Sulfhydryl-alkylating agents
-
-
-
sulfhydryl-modifying reagents
-
Tryptic fragment of bovine serum albumin
-
-
-
Ub1-72
-
cleaved ubiquitin
-
Ub1-74
-
cleaved ubiquitin
-
[(3Z,8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-(6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-3-ylsulfonyl)-1,6-diazabicyclo[6.2.0]dec-3-en-10-yl]methanol
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000042 mM
[(3Z,8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-[(1,2-dimethyl-1H-imidazol-5-yl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-3-en-10-yl]methanol
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000001 mM
[(3Z,8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-[(1-ethyl-5-methyl-1H-pyrazol-4-yl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-3-en-10-yl]methanol
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000016 mM
[(3Z,8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-[(1-propyl-1H-pyrazol-5-yl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-3-en-10-yl]methanol
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000018 mM
[(3Z,8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-[(2-methylpyridin-3-yl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-3-en-10-yl]methanol
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000022 mM
[(3Z,8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-[[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]sulfonyl]-1,6-diazabicyclo[6.2.0]dec-3-en-10-yl]methanol
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000065 mM
[(8R,9S,10S)-6-(cyclohexylsulfonyl)-9-(2',3'-dimethylbiphenyl-4-yl)-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.00046 mM
[(8R,9S,10S)-6-[(2-methylphenyl)sulfonyl]-9-[2'-methyl-3'-(trifluoromethyl)biphenyl-4-yl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000095 mM
[(8R,9S,10S)-9-(2',3'-dichlorobiphenyl-4-yl)-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000009 mM
[(8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-[(1,3-dimethyl-1H-pyrazol-5-yl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000024 mM
[(8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-[(1-methyl-1H-imidazol-2-yl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.0000005 mM
[(8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-[(1-methyl-1H-pyrazol-5-yl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.00006 mM
[(8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.0000015 mM
[(8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-[(4-methylpiperazin-1-yl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000032 mM
[(8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-[[1-(propan-2-yl)-1H-pyrazol-5-yl]sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000015 mM
[(8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-[[2-(trifluoromethyl)phenyl]sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000001 mM
[(8R,9S,10S)-9-(2',5'-dimethylbiphenyl-4-yl)-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000054 mM
[(8R,9S,10S)-9-(2'-methoxybiphenyl-4-yl)-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.00025 mM
[(8R,9S,10S)-9-(2'-methylbiphenyl-4-yl)-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000032 mM
[(8R,9S,10S)-9-(3',4'-dimethylbiphenyl-4-yl)-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.00014 mM
[(8R,9S,10S)-9-(3',5'-dimethylbiphenyl-4-yl)-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000061 mM
[(8R,9S,10S)-9-(3'-chloro-2'-methylbiphenyl-4-yl)-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000035 mM
[(8R,9S,10S)-9-(3'-fluoro-2'-methylbiphenyl-4-yl)-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.00007 mM
[(8R,9S,10S)-9-(3'-fluorobiphenyl-4-yl)-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.00007 mM
[(8R,9S,10S)-9-(3'-methoxybiphenyl-4-yl)-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.0005 mM
[(8R,9S,10S)-9-(3'-methylbiphenyl-4-yl)-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol
the inhibitor fully blocks insulin degradation in a concentration-dependent manner, while only weakly and partially inhibiting glucagon degradation. It inhibits wild-type enzyme, but does not inhibit A479L exo-site variant. It displays decreased affinity
[(8R,9S,10S)-9-(biphenyl-4-yl)-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.0004 mM
[(8R,9S,10S)-9-[3'-fluoro-2'-(trifluoromethyl)biphenyl-4-yl]-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.00017 mM
[(8R,9S,10S)-9-[4-(1,3-benzodioxol-5-yl)phenyl]-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol
half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.0029 mM
[(Z)-1-[N-3-aminopropyl]-N-(n-propyl)amino]diazen-1-ium-1,2-dolate
-
nitric oxide donors decrease both insulin and amyloid beta degrading activities of insulysin. Insulin-degrading activity is more sensitive to nitric oxide inhibition than amyloid beta degrading activity. Insulysin-mediated regulation of proteasome activity is affected similarly to insulin-degrading activity. S-nitrosylation of enzyme does not affect the insulin degradation products produced by the enzyme, nor does nitric oxide affect insulin binding to insulysin. Inhibition is noncompetitive
1,10-phenanthroline
-
-
1,10-phenanthroline
-
a Zn2+ chelator
1,10-phenanthroline
-
Zn2+, Co2+, Mn2+ and to a smaller extent Cd2+ and Fe2+ are capable of preventing the inhibition
1,10-phenanthroline
-
a Zn-chelator
ATP
-
interacts via the phosphate moiety, inhibits IDE and shifts the oligomeric equilibrium promoting the transition from tetramer to dimer and from closed to open state
ATP
-
interacts via the phosphate moiety, inhibits IDE and shifts the oligomeric equilibrium promoting the transition from tetramer to dimer and from closed to open state
ATP
-
ATP hydrolysis is a mechanism for reversion of this inhibition, however, insulin does not modify the ATPase activity of IDE
ATP
-
interacts via the phosphate moiety, inhibits IDE and shifts the oligomeric equilibrium promoting the transition from tetramer to dimer and from closed to open state
bacitracin
-
-
bacitracin
the inhibitory effect in enhanced by ATP
Co2+
-
-
Cu2+
-
-
EDTA
-
-
EDTA
-
the activation of IDE disappears upon inactivation by EDTA, which chelates the catalytic Zn2+ ion
EDTA
-
21% inhibition; 35.7% inhibition
EDTA
-
0.1 mM, wild-type, 91% residual activity, mutants H112D, H112Q, less than 2.5% residual activity
hydrogen peroxide
-
-
hydrogen peroxide
-
the oxidative burst of BV-2 microglial cells leads to oxidation of secreted IDE at Cys residues, e.g. Cys819, Cys110, Cys257, and Cys178, leading to the reduced activity after 4 h versus amyloid beta degradation, increases IDE oligomerization, and decreases IDE thermostability. Within the first 4 h of incubation at 37°C, the control and H2O2-treated enzyme does not lose any relative activity. The inhibitory response of IDE is substrate-dependent, biphasic for amyloid beta degradation but monophasic for a shorter bradykinin-mimetic substrate, mutational analysis, overview. Only Cys819 modification plays a prominent role in the change of enzyme properties
Inhibitor from rat liver homogenate
-
purification of endogenous inhibitor from rat liver
-
Inhibitor from rat liver homogenate
-
low-molecular-weight protein, order of greatest to least activity: pancreas, liver, kidney, testes, adrenal, lung, spleen, diaphragm, heart, muscle, brain, epididymal fad pad, skin
-
Insulin
-
inhibits amylin degradation, excess insulin inhibits insulin degradation
-
Insulin
-
substrate inhibition
-
Mg2+
-
stimulates cytosolic activity, inhibits particulate activity
Mg2+
-
activates, less active than Mn2+, inhibitory at above 0.05 mM
Mn2+
-
-
N-ethylmaleimide
-
-
NEM
-
-
NEM
-
modifies Cys819 and inhibits IDE
nestin
-
potently inhibits the cleavage of ubiquitin by IDE
-
nestin
-
insulin degradation activity of IDE is suppressed by about 50% by either nestin or phosphorylated vimentin, while the cleavage of bradykinin-mimetic peptide by IDE is increased 2 to 3fold
-
nestin
-
insulin degradation activity of IDE is suppressed by about 50% by either nestin or phosphorylated vimentin, while the cleavage of bradykinin-mimetic peptide by IDE is increased 2 to 3fold
-
Ni2+
-
-
nitric oxide
-
amyloid beta peptide degradation by IDE is inhibited by NO donor Sin-1
nitric oxide
-
incubation with NO donor Sin-1 results in a strong reduction of IDE activity. In vivo the activity of insulin-degrading enzyme is lowered in APP/PS1 mice, but not in APP/PS1/NOS2(-/-) mice
phosphorylated vimentin
-
insulin degradation activity of IDE is suppressed by about 50% by either nestin or phosphorylated vimentin, while the cleavage of bradykinin-mimetic peptide by IDE is increased 2 to 3fold
-
phosphorylated vimentin
-
insulin degradation activity of IDE is suppressed by about 50% by either nestin or phosphorylated vimentin, while the cleavage of bradykinin-mimetic peptide by IDE is increased 2 to 3fold
-
PMSF
-
14.4% inhibition
Proinsulin
-
-
-
Proinsulin
-
competitive
-
S-nitrosoglutathione
-
potent inhibition at physiologically relevant concentrations
S-nitrosoglutathione
-
the oxidative burst of BV-2 microglial cells leads nitrosylation of secreted IDE at Cys residues, e.g. Cys819, Cys110, Cys257, and Cys178, leading to the reduced activity versus amyloid beta degradation, increases IDE oligomerization, and decreases IDE thermostability. This inhibitory response of IDE is substrate-dependent, biphasic for amyloid beta degradation but monophasic for a shorter bradykinin-mimetic substrate, mutational analysis, overview. Only Cys819 modification plays a prominant role in the change of enzyme properties
S-nitrosoglutathione
-
inhibits IDE-mediated degradation of two IDE substrates, insulin and amyloid beta
sulfhydryl-modifying reagents
-
Drosophila, human and rat enzyme inhibited, bacterial enzyme not
-
sulfhydryl-modifying reagents
-
Drosophila, human and rat enzyme inhibited, bacterial enzyme not
-
sulfhydryl-modifying reagents
-
Drosophila, human and rat enzyme inhibited, bacterial enzyme not
-
Zn2+
-
ZnCl2
additional information
-
not: the enzyme is inhibited by cysteine protease inhibitors as well as metalloprotease inhibitors
-
additional information
-
not: aprotinin; not: pancreatic trypsin inhibitor
-
additional information
-
not: phenylmethanesulfonyl fluoride; not: phosphoramidon
-
additional information
-
not: the enzyme is inhibited by cysteine protease inhibitors as well as metalloprotease inhibitors
-
additional information
-
in patients with V97L mutation of presenilin 1, insulysin activity on the plasma membranes is reduction concomitantly with increased levels of extracellular and intracellular amyloid beta42. In the presenilin 1 V97L mutant-transfected SH-SY5Y cell line, increase of intracellular amyloid beta42 is associated with decreased expression and activity of insulysin in the cytosol and endoplasmic reticulum
-
additional information
-
amyloid beta-induced oxidation of IDE by 4-hydroxy-nonenal does not affect IDE activity in human neuroblastoma SH-SY5Y cells, but rapidly induces IDE expression
-
additional information
-
not: leupeptin; not: pepstatin
-
additional information
-
not: leupeptin
-
additional information
-
not: bestatine
-
additional information
-
not: the enzyme is inhibited by cysteine protease inhibitors as well as metalloprotease inhibitors
-
additional information
-
not: antipain; not: bestatine; not: chymostatin; not: elastatinal; not: leupeptin; not: pepstatin; not: phosphoramidon
-
additional information
-
not: overview: various amino acid derivatives, small polypeptides, indole and quinoline derivatives, dyes and dye derivatives
-
additional information
-
pepstatin-A, leupeptin, and calpains are ineffective as inhibitors, no competitive inhibition with EGF or insulin C-peptide
-
additional information
-
IDE is inhibited by metal chelators, thiol modifiers, inhibitors of cysteine protease activity and insulin, no inhibition by GTP and DMSO, poor inhibition by ATP
-
additional information
-
not: benzamidine; not: bestatine; not: phenylmethanesulfonyl fluoride
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
1-diphosphoinositol pentakisphosphate
activates, maximal 79.7fold activation
2',3'-O-(2,4,6-trinitrophenyl)adenosine triphosphate
-
about 15fold activation, 50% activation at o.0016 mM, activation is inhibited by Mg2+
2'-O-(2,4,6-trinitrophenyl) adenosine triphosphate
-
ATP-derivative TNP-ATP
3'-O-(2,4,6-trinitrophenyl) adenosine triphosphate
-
ATP-derivative TNP-ATP
5-(4-chlorophenyl)-2-[(E)-{[(5-chloro-1,2,3-thiadiazol-4-yl)methoxy]imino}methyl]cyclohexane-1,3-dione
-
direct stimulation of IDE, acts highly synergistically with ATP, Ia1 activates the degradation of amyloid beta by about 700% in presence other shorter substrates
5-diphosphoinositol pentakisphosphate
activates, maximal 94.7fold activation
alpha-synuclein
a peptide with the C-terminal 44 residues of alpha-synuclein increases insulin-degrading enzyme proteolysis to the same degree as full-length alpha-synuclein. A peptide containing the first 97 residues of alpha-synuclein does not improve insulin-degrading enzyme activity. Because the alpha-synuclein C-terminus is acidic, the interaction appears to involve electrostatic attraction with basic exosite of insulin-degrading enzyme
-
amyloid beta-peptide 1-40
-
-
-
Insulin B-chain
-
activation of reaction with substrate 2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine) and amyloid beta-protein
mercaptoethanol
-
stimulates
myoinositol 1,2,3,4,5,6-hexakisphosphate
i.e. phytic acid, maximal 72fold activation
myoinositol 1,2-bisphosphate
activates, maximal 3.1fold activation
myoinositol 1,3,4,5,6-pentakisphosphate
activates, maximal 83.3fold activation
myoinositol 1,3,4,5-tetrakisphosphate
activates, maximal 58.6fold activation
myoinositol 1,3,5-trisphosphate
activates, maximal 12.9fold activation
myoinositol 1,3-bisphosphate
activates, maximal 6.1fold activation
myoinositol 1,4,5-trisphosphate
activates, maximal 30.6fold activation
myoinositol 3-phosphate
activates, maximal 6.2fold activation
myoinositol 4,5-bisphosphate
activates, maximal 13.8fold activation
N-(3-chlorophenyl)-4-[5-(furan-2-yl)-1H-pyrazol-3-yl]piperidine-1-carboxamide
-
direct stimulation of IDE, acts highly synergistically with ATP, Ia2 activates the degradation of amyloid beta by about 400% in presence of other shorter substrates
phosphorylated vimentin
-
resveratrol
incubation with resveratrol results in a substantial increase in Abeta42 fragmentation compared to the control, signifying that the polyphenol sustains insulin-degrading enzyme-dependent degradation of Abeta42 and its fragments
Sulfhydryl-dependent enzyme
-
-
-
A23187
-
calcium ionophore, increases extracellular IDE activity, but only under conditions that also elicit cytotoxicity
A23187
-
calcium ionophore, increases extracellular IDE activity, but only under conditions that also elicit cytotoxicity
ADP
activates, the activating effect of ATP is greater than hat of ADP, which in turn is much greater than that of AMP
ADP
-
in Tris buffer, activation for substrate 2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine). Activation in decreasing order: ATP, triphosphate, ADP, AMP
ADP
-
inhibition of binding of 2,3-O-(2,4,6-trinitrophenyl)adenosine triphosphate with Ki-value 2.2 mM
AMP
activates, the activating effect of ATP is greater than hat of ADP, which in turn is much greater than that of AMP
AMP
-
in Tris buffer, activation for substrate 2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine). Activation in decreasing order: ATP, triphosphate, ADP, AMP
ATP
activates the wild-type enzyme by about 300%, mutant D426C/K899C by about 50%, ATP enhances IDE activity by inducing a direct conformational change within individual IDE molecules, overview. The activating effect of ATP is greater than that of ADP, which in turn is much greater than that of AMP. The activation of IDE by ATP might be attributable to non-specific solvent effects rather than to specific interactions with a bona fide nucleotide binding domain
ATP
-
direct stimulation of IDE, acts highly synergistically with Ia1 and Ia2. The putative ATP-binding domain is a key modulator of IDE proteolytic activity
ATP
-
50% activation at 1.4 mM, activation is inhibited by Mg2+. Inhibition of binding of 2,3-O-(2,4,6-trinitrophenyl)adenosine triphosphate with Ki-value 1.3 mM
ATP
-
in Tris buffer, up to 20fold activation for substrate 2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine), noncompetitive activator. Activation in decreasing order: ATP, triphosphate, ADP, AMP. Up to 10fold activation with substrates bradykinin, dynorphin B-9. No activation with substrates insulin or amyloid beta-protein
ATP
-
regulatory cationic binding site, 76 kDa and 56 kDa fragments of IDE, derived from cleavage with proteinase K, retain the ability to bind ATP, 4fold activation at 4 mM of 56 kDa fragment, poor activation of the 76 kDa enzyme fragment, overview
ATP
-
40fold activation for wild-type
bradykinin
-
-
bradykinin
-
activation of reaction with substrate 2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine) and amyloid beta-protein
bradykinin
-
4fold activation for wild-type
dynorphin A-17
-
activation of reaction with substrate 2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine) and amyloid beta-protein
dynorphin B-13
-
activation of reaction with substrate 2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine) and amyloid beta-protein
dynorphin B-9
-
activation of reaction with substrate 2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine) and amyloid beta-protein
dynorphin B-9
-
2.5fold increase in amyloid beta peptide hydrolysis
nestin
-
insulin degradation activity of IDE is suppressed by about 50% by either nestin or phosphorylated vimentin, while the cleavage of bradykinin-mimetic peptide by IDE is increased 2 to 3fold
-
nestin
-
insulin degradation activity of IDE is suppressed by about 50% by either nestin or phosphorylated vimentin, while the cleavage of bradykinin-mimetic peptide by IDE is increased 2 to 3fold
-
phosphorylated vimentin
-
insulin degradation activity of IDE is suppressed by about 50% by either nestin or phosphorylated vimentin, while the cleavage of bradykinin-mimetic peptide by IDE is increased 2 to 3fold
-
phosphorylated vimentin
-
insulin degradation activity of IDE is suppressed by about 50% by either nestin or phosphorylated vimentin, while the cleavage of bradykinin-mimetic peptide by IDE is increased 2 to 3fold
-
Somatostatin
-
somatostatin binding to IDE brings about a concentration-dependent structural change of the secondary and tertiary structure of the enzyme, revealing two possible binding sites. The higher affinity binding site disappears upon inactivation of IDE by ethylenediaminetetraacetic acid, which chelates the catalytic Zn2+ ion
Somatostatin
enhances the proteolytic processing of a synthetic beta-amyloid-peptide. In addition to being a substrate, somatostatin is also able to bind to two additional exosites, which play different roles according to the size of the substrate and its binding mode to the catalytic cleft of the enzyme. One exosite, which displays high affinity for somatostatin, regulates only the interaction of insulin-degrading-enzyme with larger substrates (such as insulin and beta-amyloid1-40) in a differing fashion according to their various modes of binding to the enzyme. A second exosite, which is involved in the regulation of enzymatic processing by the enzyme of all substrates investigated (including a 10-25 amino acid long amyloid-like peptide, bradykinin and somatostatin itself), probably acts through the alteration of an open-closed equilibrium
Triphosphate
-
-
Triphosphate
-
in Tris buffer, up to 20fold activation for substrate 2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine), noncompetitive activator. Activation in decreasing order: ATP, triphosphate, ADP, AMP. Up to 10fold activation with substrates bradykinin, dynorphin B-9. No activation with substrates insulin or amyloid beta-protein
Triphosphate
-
inhibition of binding of 2,3-O-(2,4,6-trinitrophenyl)adenosine triphosphate with Ki-value 0.9 mM
additional information
purine nucleotide triphosphates are better activators than pyrimidine nucleotide triphosphates
-
additional information
-
purine nucleotide triphosphates are better activators than pyrimidine nucleotide triphosphates
-
additional information
-
amyloid beta-induced oxidation of IDE by 4-hydroxy-nonenal does not affect IDE activity in human neuroblastoma SH-SY5Y cells, but rapidly induces IDE expression
-
additional information
-
synthesis and analysis of synthetic small-molecule activators, structure-activity relationships, overview
-
additional information
-
fibrillar amyloid beta-peptide induces the enzyme in astrocytes through activation of a MAPK cascade via ERK1/2
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
0.0056 - 0.0076
(7-methoxycoumarin-4-yl)acetyl-KLVFFAEDK(Dnp)-OH
0.0099
(7-methoxycoumarin-4-yl)acetyl-RPPGFSAFK(2,4-dinitrophenyl)-OH
37°C, pH not specified in the publication
0.014 - 0.204
2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine)
0.0047 - 0.0049
7-methoxycoumarin-4-yl-acetyl-RPPGFSAFK-2,4-dinitrophenyl
0.0066 - 21.3
Abz-GGFLRKHGQ-EDDnp
0.0059 - 0.0254
Abz-GGFLRKHGQEDDnp
0.0111
Abz-Gly-Gly-Leu-Arg-Lys-His-Gly-Gln-EDDnp
37°C, pH 7.4, without activator
0.219
Abz-SEKKDNYIIKGV-nitroY-OH
-
pH 9.2, 37°C, recombinant enzyme
0.08
amyloid beta
-
pH 8.0, 37°C, wild-type enzyme
-
0.0028
amyloid beta-peptide 1-40
pH not specified in the publication, temperature not specified in the publication
-
0.0023
amyloid beta-peptide 1-42
pH not specified in the publication, temperature not specified in the publication
-
0.025 - 0.027
amyloid beta-peptide1-40
-
0.00123 - 0.00252
amyloid beta-protein
-
2.5
amyloid beta1-40
-
pH 7.3, 37°C
-
4.2
bradykinin
-
pH 7.3, 37°C
1.2 - 2.3
Dabcyl-Tyr-Glu-Val-His-His-Gln-Lys-Leu-Val-Phe-Phe-Ala-Glu-Asp-Val-Gly-Glu(EDANS)-NH2
0.0000158
desalanine-insulin
-
-
-
0.000176
desdipeptide-proinsulin
-
-
-
0.000055
desnonapeptide-proinsulin
-
-
-
0.000044
destridecapeptide-proinsulin
-
-
-
0.000003 - 0.02
Insulin
-
0.000055
insulin-like peptide 3
-
pH 7.7, 37°C
-
7.3
kallidin
-
pH 7.3, 37°C
0.0000244
monoarginine-insulin
-
diarginine-insulin
-
0.0002342 - 0.0008572
Proinsulin
-
7.5
Somatostatin
-
pH 7.3, 37°C
additional information
additional information
-
0.0056
(7-methoxycoumarin-4-yl)acetyl-KLVFFAEDK(Dnp)-OH
pH 7.0, 37°C, mutant enzyme R183Q
0.0076
(7-methoxycoumarin-4-yl)acetyl-KLVFFAEDK(Dnp)-OH
pH 7.0, 37°C, wild-type enzyme
0.014
2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine)
-
mutant E111L, pH 7.3
0.0156
2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine)
-
mutant E111V, pH 7.3
0.0274
2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine)
-
mutant E111F, pH 7.3
0.0287
2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine)
-
wild-type, K0.5-value, pH 7.3
0.083
2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine)
-
mutant H112D, pH 7.3
0.158
2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine)
-
mutant H112Q, pH 7.3
0.204
2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine)
-
mutant E111A, pH 7.3
0.0047
7-methoxycoumarin-4-yl-acetyl-RPPGFSAFK-2,4-dinitrophenyl
pH 7.0, 37°C, wild-type enzyme
0.0049
7-methoxycoumarin-4-yl-acetyl-RPPGFSAFK-2,4-dinitrophenyl
pH 7.0, 37°C, mutant enzyme R183Q
0.0066
Abz-GGFLRKHGQ-EDDnp
-
pH 7.4, temperature not specified in the publication, mutant DELTAC lacking the C-terminal region
0.0068
Abz-GGFLRKHGQ-EDDnp
-
pH 7.4, temperature not specified in the publication, mutant T609F, Vmax: 2.6 nmol/min/mg
0.0085
Abz-GGFLRKHGQ-EDDnp
-
pH 7.4, temperature not specified in the publication, mutant I374S, Vmax: 3.45 nmol/min/mg
0.00861
Abz-GGFLRKHGQ-EDDnp
-
pH 7.4, temperature not specified in the publication, mutant V360S, Vmax: 2 nmol/min/mg
0.0091
Abz-GGFLRKHGQ-EDDnp
-
pH 7.4, 37°C, IDE:IDE mutant E111F/Y609F
0.0109
Abz-GGFLRKHGQ-EDDnp
-
pH 7.4, 37°C, mutant Y609F IDE:IDE mutant E111F
0.0113
Abz-GGFLRKHGQ-EDDnp
-
pH 7.4, 37°C, mutant Y609F IDE:IDE mutant H112Q
0.0135
Abz-GGFLRKHGQ-EDDnp
-
pH 7.4, 37°C, IDE:IDE mutant H112Q/Y609F
0.0148
Abz-GGFLRKHGQ-EDDnp
-
pH 7.4, 37°C, mutant Y609F IDE:IDE mutant E111F/Y609F
0.01587
Abz-GGFLRKHGQ-EDDnp
-
pH 7.4, temperature not specified in the publication, wild-type, Vmax: 35.5 nmol/min/mg
0.0192
Abz-GGFLRKHGQ-EDDnp
-
pH 7.4, 37°C, mutant Y609F IDE:IDE mutant H112Q/Y609F
0.0215
Abz-GGFLRKHGQ-EDDnp
-
pH 7.4, temperature not specified in the publication, wild-type
0.0217
Abz-GGFLRKHGQ-EDDnp
-
pH 7.4, 37°C, IDE:IDE mutant E111F
0.0232
Abz-GGFLRKHGQ-EDDnp
-
pH 7.4, 37°C, IDE:IDE mutant H112Q
0.0268
Abz-GGFLRKHGQ-EDDnp
-
pH 7.4, 37°C, mutant Y609F IDE:IDE mutant Y609F
0.0315
Abz-GGFLRKHGQ-EDDnp
-
pH 7.4, 37°C, IDE:IDE, wild-type
0.033
Abz-GGFLRKHGQ-EDDnp
pH 7.7, 37°C, wild-type enzyme
0.035
Abz-GGFLRKHGQ-EDDnp
pH 7.7, 37°C, mutant enzyme K364A
0.035
Abz-GGFLRKHGQ-EDDnp
pH 7.7, 37°C, mutant enzyme S137A
0.043
Abz-GGFLRKHGQ-EDDnp
pH 7.7, 37°C, mutant enzyme K898A
0.044
Abz-GGFLRKHGQ-EDDnp
pH 7.7, 37°C, mutant enzyme F807A
0.103
Abz-GGFLRKHGQ-EDDnp
pH 7.7, 37°C, mutant enzyme D426A
9.6
Abz-GGFLRKHGQ-EDDnp
-
wild-type, pH 7.4, temperature not specified in the publication
17.3
Abz-GGFLRKHGQ-EDDnp
-
mutant K898A/K899A/S901A, pH 7.4, temperature not specified in the publication
21.3
Abz-GGFLRKHGQ-EDDnp
-
mutant R429S, pH 7.4, temperature not specified in the publication
0.0059
Abz-GGFLRKHGQEDDnp
-
pH 7.4, 37°C, 56 kDa detagged fragment of recombinant His6-tagged enzyme
0.0075
Abz-GGFLRKHGQEDDnp
-
pH 7.4, 37°C, 76 kDa detagged fragment of recombinant His6-tagged enzyme
0.0254
Abz-GGFLRKHGQEDDnp
-
pH 7.4, 37°C, recombinant His6-tagged full-length enzyme
0.025
amyloid beta-peptide1-40
recombinant wild-type enzyme, pH 7.4, 37°C
-
0.027
amyloid beta-peptide1-40
recombinant mutant D426C/K899C, pH 7.4, 37°C
-
0.00123
amyloid beta-protein
isoform 15a-IDE, pH 7.4, 37°C
-
0.00252
amyloid beta-protein
isoform 15b-IDE, pH 7.4, 37°C
-
1.2
Dabcyl-Tyr-Glu-Val-His-His-Gln-Lys-Leu-Val-Phe-Phe-Ala-Glu-Asp-Val-Gly-Glu(EDANS)-NH2
-
pH 7.3, 37°C, presence of 0.04 mM somatostatin
2.3
Dabcyl-Tyr-Glu-Val-His-His-Gln-Lys-Leu-Val-Phe-Phe-Ala-Glu-Asp-Val-Gly-Glu(EDANS)-NH2
-
pH 7.3, 37°C
0.000003
Insulin
-
procine substrate
-
0.000052
Insulin
-
pH 7.7, 37°C
-
0.000058
Insulin
-
pH 7.4, 37°C
-
0.0000657
Insulin
isoform 15a-IDE, pH 7.4, 37°C
-
0.0001
Insulin
-
pH not specified in the publication, temperature not specified in the publication
-
0.000222
Insulin
isoform 15b-IDE, pH 7.4, 37°C
-
0.00025 - 0.00065
Insulin
-
Km is species-dependent
-
0.00025 - 0.00065
Insulin
-
Km is species-dependent
-
0.00025 - 0.00065
Insulin
-
Km is species-dependent
-
0.00025 - 0.00065
Insulin
-
Km is species-dependent
-
0.00025 - 0.00065
Insulin
-
Km is species-dependent
-
0.00025 - 0.00065
Insulin
Frog
-
Km is species-dependent
-
0.005 - 0.007
Insulin
-
-
-
0.02
Insulin
pH 7.4, 37°C
-
0.0002342
Proinsulin
-
cleaved
-
0.0008572
Proinsulin
-
-
-
additional information
additional information
-
no relation between Km and the chemical dissimilarity between bovine insulin and endogenous insulin of the species
-
additional information
additional information
-
no relation between Km and the chemical dissimilarity between bovine insulin and endogenous insulin of the species
-
additional information
additional information
-
no relation between Km and the chemical dissimilarity between bovine insulin and endogenous insulin of the species
-
additional information
additional information
-
no relation between Km and the chemical dissimilarity between bovine insulin and endogenous insulin of the species
-
additional information
additional information
-
no relation between Km and the chemical dissimilarity between bovine insulin and endogenous insulin of the species
-
additional information
additional information
Frog
-
no relation between Km and the chemical dissimilarity between bovine insulin and endogenous insulin of the species
-
additional information
additional information
-
kinetics, overview
-
additional information
additional information
-
with substrate 2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine), enzyme exhibits allosteric kinetics
-
additional information
additional information
-
amyloid beta degradation kinetics in presence or absence of activators
-
additional information
additional information
-
kinetics of wild-type IDE, IDE mutants, and IDE modified at Cys residues by H2O2 or S-nitrosoglutathione, with substrate amyloidbeta, overview. IDE exhibits substantially different enzyme kinetic parameters with the longer peptide amyloidbeta as compared with a shorter peptide substrate, the bradykinin-mimetic substrate V
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
1.2 - 7.5
(7-methoxycoumarin-4-yl)acetyl-KLVFFAEDK(Dnp)-OH
0.028
(7-methoxycoumarin-4-yl)acetyl-NPPGFSAFK-2,4-dinitrophenyl
-
pH not specified in the publication, 37°C
0.29 - 1.1
(7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH
0.23
(7-methoxycoumarin-4-yl)acetyl-RPPGFSAFK(2,4-dinitrophenyl)-OH
37°C, pH not specified in the publication
0.088 - 0.24
(7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH
2 - 162600
2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine)
1.2 - 6.5
7-methoxycoumarin-4-yl-acetyl-RPPGFSAFK-2,4-dinitrophenyl
0.003 - 2.42
Abz-GGFLRKHGQ-EDDnp
0.72 - 104
Abz-GGFLRKHGQEDDnp
70
amyloid beta
-
pH 8.0, 37°C, wild-type enzyme
-
0.0022
amyloid beta-peptide 1-40
pH not specified in the publication, temperature not specified in the publication
-
0.0004
amyloid beta-peptide 1-42
pH not specified in the publication, temperature not specified in the publication
-
8 - 20
amyloid beta-peptide1-40
-
0.17 - 0.88
amyloid beta-protein
-
8
amyloid beta1-40
-
pH 7.3, 37°C
-
61 - 62.7
Dabcyl-Tyr-Glu-Val-His-His-Gln-Lys-Leu-Val-Phe-Phe-Ala-Glu-Asp-Val-Gly-Glu(EDANS)-NH2
0.0025
insulin-like peptide 3
-
pH 7.7, 37°C
-
10
protein ANP
-
pH not specified in the publication, 37°C
-
0.2
protein BNP
-
pH not specified in the publication, 37°C
-
20
protein CNP
-
pH not specified in the publication, 37°C
-
0.1
protein DNP
-
pH not specified in the publication, 37°C
-
0.38
Somatostatin
-
pH 7.3, 37°C
2
urodilatin
-
pH not specified in the publication, 37°C
-
1.2
(7-methoxycoumarin-4-yl)acetyl-KLVFFAEDK(Dnp)-OH
pH 7.0, 37°C, mutant enzyme R183Q
7.5
(7-methoxycoumarin-4-yl)acetyl-KLVFFAEDK(Dnp)-OH
pH 7.0, 37°C, wild-type enzyme
0.29
(7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme F820Y
0.298
(7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme Y150K
0.33
(7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme 141A
0.338
(7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme Y150F
0.45
(7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme Y150W
0.53
(7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme F202D
0.57
(7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme W199Y
0.57
(7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, wild-type enzyme
0.625
(7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme 141W
0.72
(7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme F115Y
0.725
(7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme F115A
0.73
(7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme F115W
0.735
(7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme F202Y
0.78
(7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme 141Y
0.803
(7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme F202W
0.85
(7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme F820W
1.1
(7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme Y150F
0.088
(7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme W199K
0.095
(7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme Y150K
0.097
(7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme F202D
0.097
(7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme F202K
0.1
(7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme F141W
0.108
(7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme F820Y
0.123
(7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme F141N
0.143
(7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme Y150W
0.148
(7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme F202W
0.16
(7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme F820W
0.16
(7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme W199Y
0.17
(7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme F202N
0.177
(7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme W199N
0.178
(7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme F141Y
0.18
(7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme W199A
0.198
(7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, wild-type enzyme
0.2
(7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme F115Y
0.22
(7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme F141A
0.22
(7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme Y150F
0.24
(7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme F202Y
0.24
(7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH
pH 7.3, 37°C, mutant enzyme W199F
2 - 3.7
2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine)
-
mutant H112D, pH 7.3
2.4
2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine)
-
mutant E111V, pH 7.3
6.5
2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine)
-
mutant E111L, pH 7.3
11.4
2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine)
-
mutant E111F, pH 7.3
17.5
2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine)
-
mutant E111A, pH 7.3
1953
2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine)
-
mutant H112Q, pH 7.3
162600
2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine)
-
wild-type, pH 7.3
1.2
7-methoxycoumarin-4-yl-acetyl-RPPGFSAFK-2,4-dinitrophenyl
pH 7.0, 37°C, mutant enzyme R183Q
6.5
7-methoxycoumarin-4-yl-acetyl-RPPGFSAFK-2,4-dinitrophenyl
pH 7.0, 37°C, wild-type enzyme
0.003
Abz-GGFLRKHGQ-EDDnp
-
pH 7.4, 37°C, mutant Y609F IDE:IDE mutant E111F/Y609F
0.01
Abz-GGFLRKHGQ-EDDnp
-
pH 7.4, 37°C, IDE:IDE mutant E111F/Y609F
0.01
Abz-GGFLRKHGQ-EDDnp
-
pH 7.4, 37°C, mutant Y609F IDE:IDE mutant E111F
0.01
Abz-GGFLRKHGQ-EDDnp
-
pH 7.4, temperature not specified in the publication, mutant DELTAC lacking the C-terminal region
0.03
Abz-GGFLRKHGQ-EDDnp
-
pH 7.4, 37°C, IDE:IDE mutant H112Q/Y609F
0.03
Abz-GGFLRKHGQ-EDDnp
-
pH 7.4, 37°C, mutant Y609F IDE:IDE mutant Y609F
0.043
Abz-GGFLRKHGQ-EDDnp
-
pH 7.4, temperature not specified in the publication, wild-type
0.05
Abz-GGFLRKHGQ-EDDnp
-
pH 7.4, 37°C, mutant Y609F IDE:IDE mutant H112Q
0.06
Abz-GGFLRKHGQ-EDDnp
-
pH 7.4, 37°C, mutant Y609F IDE:IDE mutant H112Q/Y609F
0.078
Abz-GGFLRKHGQ-EDDnp
-
mutant R429S, pH 7.4, temperature not specified in the publication
0.086
Abz-GGFLRKHGQ-EDDnp
-
wild-type, pH 7.4, temperature not specified in the publication
0.12
Abz-GGFLRKHGQ-EDDnp
-
pH 7.4, 37°C, IDE:IDE mutant H112Q
0.14
Abz-GGFLRKHGQ-EDDnp
-
pH 7.4, 37°C, IDE:IDE, wild-type
0.258
Abz-GGFLRKHGQ-EDDnp
-
mutant K898A/K899A/S901A, pH and temperature not specified in the publication
1.13
Abz-GGFLRKHGQ-EDDnp
pH 7.7, 37°C, mutant enzyme D426A
1.68
Abz-GGFLRKHGQ-EDDnp
pH 7.7, 37°C, mutant enzyme F807A
1.7
Abz-GGFLRKHGQ-EDDnp
pH 7.7, 37°C, wild-type enzyme
1.83
Abz-GGFLRKHGQ-EDDnp
pH 7.7, 37°C, mutant enzyme K364A
1.97
Abz-GGFLRKHGQ-EDDnp
pH 7.7, 37°C, mutant enzyme S137A
2.42
Abz-GGFLRKHGQ-EDDnp
pH 7.7, 37°C, mutant enzyme K898A
0.72
Abz-GGFLRKHGQEDDnp
-
pH 7.4, 37°C, 56 kDa detagged fragment of recombinant His6-tagged enzyme
0.77
Abz-GGFLRKHGQEDDnp
-
pH 7.4, 37°C, 76 kDa detagged fragment of recombinant His6-tagged enzyme
93.17
Abz-GGFLRKHGQEDDnp
-
pH 7.4, 37°C, recombinant His6-tagged full-length enzyme
104
Abz-GGFLRKHGQEDDnp
-
pH 7.4, 37°C, recombinant His6-tagged full-length enzyme
8
amyloid beta-peptide1-40
recombinant wild-type enzyme, pH 7.4, 37°C
-
8
amyloid beta-peptide1-40
-
recombinant wild-type enzyme, pH 7.4, 37°C
-
20
amyloid beta-peptide1-40
recombinant mutant D426C/K899C, pH 7.4, 37°C
-
20
amyloid beta-peptide1-40
-
recombinant mutant D426C/K899C, pH 7.4, 37°C
-
0.17
amyloid beta-protein
isoform 15b-IDE, pH 7.4, 37°C
-
0.88
amyloid beta-protein
isoform 15a-IDE, pH 7.4, 37°C
-
61
Dabcyl-Tyr-Glu-Val-His-His-Gln-Lys-Leu-Val-Phe-Phe-Ala-Glu-Asp-Val-Gly-Glu(EDANS)-NH2
-
pH 7.3, 37°C, presence of 0.04 mM somatostatin
62.7
Dabcyl-Tyr-Glu-Val-His-His-Gln-Lys-Leu-Val-Phe-Phe-Ala-Glu-Asp-Val-Gly-Glu(EDANS)-NH2
-
pH 7.3, 37°C
0.017
Insulin
isoform 15b-IDE, pH 7.4, 37°C
-
0.025
Insulin
isoform 15a-IDE, pH 7.4, 37°C
-
0.048
Insulin
pH 7.4, 37°C
-
0.05
Insulin
-
pH 7.7, 37°C
-
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0.0004
((((S)-1-benzylcarbamoyl-2-(1H-imidazol-4-yl)-ethylcarbamoyl)-methyl)-(3-phenyl-propyl)-amino)-acetic acid
Homo sapiens
in HEPES 50 mM, NaCl 100 mM, pH 7.4, at 37°C
0.0005
((((S)-2-(1H-imidazol-4-yl)-1-(3-methyl-(1,2,4)oxadiazol-5-yl)-ethylcarbamoyl)-methyl)-(3-phenyl-propyl)-amino)-acetic acid
Homo sapiens
in HEPES 50 mM, NaCl 100 mM, pH 7.4, at 37°C
0.0001
((((S)-2-(1H-imidazol-4-yl)-1-methylcarbamoylethylcarbamoyl)-methyl)-(3-phenyl-propyl)-amino)-acetic acid
Homo sapiens
in HEPES 50 mM, NaCl 100 mM, pH 7.4, at 37°C
0.0016
((((S)-2-hydroxy-1-(1H-imidazol-4-ylmethyl)-ethylcarbamoyl)-methyl)-(3-phenyl-propyl)-amino)-acetic acid
Homo sapiens
in HEPES 50 mM, NaCl 100 mM, pH 7.4, at 37°C
0.0014
(benzyl-(((S)-1-benzylcarbamoyl-2-(1H-imidazol-4-yl)-ethylcarbamoyl)-methyl)-amino)-acetic acid
Homo sapiens
in HEPES 50 mM, NaCl 100 mM, pH 7.4, at 37°C
0.0014
(benzyl-(((S)-1-carbamoyl-2-(1H-imidazol-4-yl)-ethylcarbamoyl)-methyl)-amino)-acetic acid
Homo sapiens
in HEPES 50 mM, NaCl 100 mM, pH 7.4, at 37°C
0.0069
(benzyl-(((S)-1-dimethylcarbamoyl-2-(1H-imidazol-4-yl)-ethylcarbamoyl)-methyl)-amino)-acetic acid
Homo sapiens
in HEPES 50 mM, NaCl 100 mM, pH 7.4, at 37°C
0.0006
(benzyl-(((S)-2-(1H-imidazol-4-yl)-1-methylcarbamoylethylcarbamoyl)-methyl)-amino)-acetic acid
Homo sapiens
in HEPES 50 mM, NaCl 100 mM, pH 7.4, at 37°C
0.0041
(benzyl-(((S)-2-hydroxy-1-(1H-imidazol-4-ylmethyl)-ethylcarbamoyl)-methyl)-amino)-acetic acid
Homo sapiens
in HEPES 50 mM, NaCl 100 mM, pH 7.4, at 37°C
0.0029
(S)-2-(2-((4-tert-butyl-benzyl)-carboxymethyl-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
Homo sapiens
in HEPES 50 mM, NaCl 100 mM, pH 7.4, at 37°C
0.0125
(S)-2-(2-(benzyl-(2-hydroxy-3,4-dioxo-cyclobut-1-enyl)-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
Homo sapiens
in HEPES 50 mM, NaCl 100 mM, pH 7.4, at 37°C
0.0003
(S)-2-(2-(benzyl-carboxymethyl-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid isopropyl ester
Homo sapiens
in HEPES 50 mM, NaCl 100 mM, pH 7.4, at 37°C
0.0029
(S)-2-(2-(benzyl-carboxymethyl-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
Homo sapiens
in HEPES 50 mM, NaCl 100 mM, pH 7.4, at 37°C
0.0008
(S)-2-(2-(benzyl-carboxymethyl-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid tert-butyl ester
Homo sapiens
in HEPES 50 mM, NaCl 100 mM, pH 7.4, at 37°C
0.0006
(S)-2-(2-(benzyl-carboxymethyl-amino)-acetylamino)-3-(3H-imidazol-4-yl)-propionic acid isobutyl ester
Homo sapiens
in HEPES 50 mM, NaCl 100 mM, pH 7.4, at 37°C
0.0363
(S)-2-(2-(benzyl-carboxymethyl-amino)-acetylamino)-5-guanidino-pentanoic acid methyl ester
Homo sapiens
in HEPES 50 mM, NaCl 100 mM, pH 7.4, at 37°C
0.0032
(S)-2-(2-(benzyl-hydroxycarbamoylmethyl-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
Homo sapiens
in HEPES 50 mM, NaCl 100 mM, pH 7.4, at 37°C
0.0006
(S)-2-(2-(carboxymethyl-(1-methyl-3-phenyl-propyl)-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
Homo sapiens
in HEPES 50 mM, NaCl 100 mM, pH 7.4, at 37°C
0.0012
(S)-2-(2-(carboxymethyl-(2-(1H-indol-3-yl)-ethyl)-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
Homo sapiens
in HEPES 50 mM, NaCl 100 mM, pH 7.4, at 37°C
0.001
(S)-2-(2-(carboxymethyl-(3-phenyl-propyl)-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
Homo sapiens
in HEPES 50 mM, NaCl 100 mM, pH 7.4, at 37°C
0.0004
(S)-2-(2-(carboxymethyl-(3-phenyl-propyl)-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid tert-butyl ester
Homo sapiens
in HEPES 50 mM, NaCl 100 mM, pH 7.4, at 37°C
0.0025
(S)-2-(2-(carboxymethyl-(4-fluoro-benzyl)-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
Homo sapiens
in HEPES 50 mM, NaCl 100 mM, pH 7.4, at 37°C
0.0017
(S)-2-(2-(carboxymethyl-(4-methyl-benzyl)-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
Homo sapiens
in HEPES 50 mM, NaCl 100 mM, pH 7.4, at 37°C
0.0006
(S)-2-(2-(carboxymethyl-(4-phenyl-butyl)-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
Homo sapiens
in HEPES 50 mM, NaCl 100 mM, pH 7.4, at 37°C
0.002
(S)-2-(2-(carboxymethyl-(4-trifluoromethyl-benzyl)-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
Homo sapiens
in HEPES 50 mM, NaCl 100 mM, pH 7.4, at 37°C
0.0004
(S)-2-(2-(carboxymethyl-(n-hexyl)-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
Homo sapiens
in HEPES 50 mM, NaCl 100 mM, pH 7.4, at 37°C
0.0012
(S)-2-(2-(carboxymethyl-naphthalen-2-ylmethyl-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
Homo sapiens
in HEPES 50 mM, NaCl 100 mM, pH 7.4, at 37°C
0.0014
(S)-2-(2-(carboxymethyl-phenethyl-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
Homo sapiens
in HEPES 50 mM, NaCl 100 mM, pH 7.4, at 37°C
0.0063
(S)-2-(2-(carboxymethyl-pyridin-4-ylmethyl-amino)-acetylamino)-3-(1H-imidazol-4-yl)-propionic acid methyl ester
Homo sapiens
in HEPES 50 mM, NaCl 100 mM, pH 7.4, at 37°C
0.0036
3-(((S)-1-methoxy-1-oxo-3-imidazol-2-yl)carbamoyl)-1,2,3,4-tetrahydroisoquinoline-2-ethanoic acid
Homo sapiens
in HEPES 50 mM, NaCl 100 mM, pH 7.4, at 37°C
0.00006
Ac-EWRFCGdPPECLYLVCG-NH2(Cys5-Cys10 disulfide)
Mus musculus
pH 7.5, 23°C
0.000077
Ac-EWRFCGGGdPPECLYLVCG-NH2(Cys5-Cys12-disulfide)
Mus musculus
pH 7.5, 23°C
0.00023
EALYLVCG-NH2
Mus musculus
pH 7.5, 23°C
0.00017
EALYLVCGdPPFRWE-NH2
Mus musculus
pH 7.5, 23°C
0.000022
EWRF-cyclo(DGdPPEDap)LYLVCG-NH2
Mus musculus
pH 7.5, 23°C
0.000044
EWRF-cyclo(DGGGdPPEDap)LYLVCG-NH2
Mus musculus
pH 7.5, 23°C
0.000601
EWRFdPPEALY-NH2
Mus musculus
pH 7.5, 23°C
0.000086
EWRFdPPEALYLV-NH2
Mus musculus
pH 7.5, 23°C
0.0003
EWRFGGEALYLVCG-NH2
Mus musculus
pH 7.5, 23°C
0.9
hydrogen peroxide
Homo sapiens
-
pH 8.0, 37°C
0.0000444
InsL3
Rattus norvegicus
-
pH not specified in the publication, temperature not specified in the publication
-
0.000018
methyl [(2S)-2-(5-[5-[4-([(2S)-2-[(3S)-3-amino-2-oxopiperidin-1-yl]-2-cyclohexylacetyl]amino)phenyl]pentyl]-2-fluorophenyl)-3-(quinolin-3-yl)propyl]carbamate
Homo sapiens
37°C, pH 7.5
0.000015
methyl [(2S)-2-[4-([5-[4-([(2S)-2-[(3S)-3-amino-2-oxopiperidin-1-yl]-2-cyclohexylacetyl]amino)phenyl]pentyl]oxy)phenyl]-3-(quinolin-3-yl)butyl]carbamate
Homo sapiens
37°C, pH 7.5
0.04
protein ANP
Homo sapiens
-
pH not specified in the publication, 37°C
-
0.12
protein BNP
Homo sapiens
-
pH not specified in the publication, 37°C
-
0.07
protein CNP
Homo sapiens
-
pH not specified in the publication, 37°C
-
1.3
protein DNP
Homo sapiens
-
pH not specified in the publication, 37°C
-
0.000182
relaxin
Rattus norvegicus
-
pH not specified in the publication, temperature not specified in the publication
-
0.0000537
relaxin-3
Rattus norvegicus
-
pH not specified in the publication, temperature not specified in the publication
-
1.2
S-nitrosoglutathione
Homo sapiens
-
pH 8.0, 37°C
0.09
ubiquitin
Homo sapiens
-
pH not specified in the publication, 37°C
0.8
urodilatin
Homo sapiens
-
pH not specified in the publication, 37°C
-
0.11
bacitracin
Homo sapiens
recombinant wild-type enzyme, in in presence of ATP
0.18
bacitracin
Homo sapiens
recombinant mutant D426C/K899C, in in presence of ATP
0.2
bacitracin
Homo sapiens
recombinant mutant D426C/K899C, in absence of ATP
0.4
bacitracin
Homo sapiens
recombinant wild-type enzyme, in absence of ATP
0.001
Ub1-72
Homo sapiens
-
pH not specified in the publication, 37°C
-
0.1
Ub1-72
Homo sapiens
-
pH not specified in the publication, 37°C
-
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malfunction
-
deficiency in IDE function is associated with Alzheimer's disease and type 2 diabetes mellitus pathology. IDE levels are decreased in type 2 diabetes mellitus. Regulation of IDE by PPARgamma and their roles in Alzheimer's disease and type 2 diabetes mellitus pathology
malfunction
-
genetic variants in the insulin-degrading enzyme gene are associated with metabolic syndrome in Chinese elders, relationship between the IDE gene and the development of metabolis syndrome, overview
malfunction
-
hypocatabolism of the amyloid beta-protein by insulin-degrading enzyme is implicated in the pathogenesis of Alzheimer's disease
malfunction
IDE catalyzes the degradation of the monomeric forms of Alzheimer amyloid beta peptides, which is critical for preventing the progression of Alzheimer's disease, overview
malfunction
-
reduced neuronal expression of insulin-degrading enzyme in the left and right dorsolateral prefrontal cortex, but not in other brain areas investigated, of haloperidol-treated patients or patients with chronic schizophrenia. Reduced cortical IDE expression might be part of the disturbed insulin signaling cascades found in schizophrenia. Furthermore, it might contribute to the altered metabolism of certain neuropeptides, IGF-I and IGF-II, betab-endorphin, in schizophrenia
malfunction
-
reduced neuronal expression of insulin-degrading enzyme in the left and right dorsolateral prefrontal cortex, but not in other brain areas investigated, of haloperidol-treated rats
malfunction
-
susceptibility of Goto-Kakizaki rats to diabetes due to IDE polymorphisms
malfunction
-
reduction of IDE expression diminishes the ability of natriuretic peptides ANP and BNP to stimulate natriuretic peptide receptor NPR-B
malfunction
enzyme downregulation impairs SHSY5Y cell proliferation and triggers cell death. Enzyme inhibition is accompanied by a decrease of the poly-ubiquitinated protein content and co-immunoprecipitates with proteasome and ubiquitin in SHSY5Y cells
malfunction
loss of enzyme function favors insulin resistance, a hallmark of diabetes mellitus type II. Down-regulation of the enzyme provokes reduction of tissue growth and sensitizes developmental timing and metabolism to high-sucrose diets
metabolism
-
IDE levels are significantly inversely correlated with plasma insulin, fasting blood glucose, triglyceride, total cholesterol, low-density lipoprotein, but not high-density lipoprotein, indicating IDE is possibly involved in insulin turnover and its effects on carbohydrate and lipid metabolism, overview
metabolism
-
IDE plays a primary role in insulin degradation and cellular insulin processing and therefore affects glucose and lipid metabolism
metabolism
-
palmitic acid and docosahexaenoic acid opposingly regulate the expression of insulin-degrading enzyme in neurons
metabolism
the enzyme can modulate Drosophila insulin-like peptide 2 levels, thereby restricting activation of the phosphatidylinositol-3-phosphate kinase pathway and promoting activation of Drosophila forkhead box, subgroup O transcription factor
metabolism
ATP regulates insulin-degrading enzyme-dependent degradation of insulin, but the addition of Mg2+ abolishes the regulation
metabolism
inhibition of insulin-degrading enzyme does not increase islet amyloid deposition in vitro
metabolism
knockout and genetic studies link insulin-degrading enzyme to Alzheimer's disease and type-2 diabetes
metabolism
overexpression of pitrilysin protects insulinoma cells from human islet amyloid polypeptide-induced apoptosis
metabolism
the enzyme activates ubiquitin and promotes the formation of K48 and K63 diubiquitin
metabolism
the enzyme modulates blood glucose levels by cleaving insulin, a hormone that promotes glucose clearance. It also degrades glucagon, a hormone that elevates glucose levels and opposes the effect of insulin
metabolism
the enzyme plays a key role in type-2 diabetes
physiological function
-
IDE is a ubiquitously expressed metalloproteinase responsible for the intracellular degradation of insulin, but possibly also for the cellular proteolysis of relaxin, InsL3 and relaxin-3
physiological function
-
IDE is an important protease responsible for the degradation of amyloid-beta in neural cells
physiological function
-
IDE is important in maintaining insulin levels
physiological function
-
IDE is important in maintaining insulin levels and in insulin catabolism
physiological function
-
IDE is important in maintaining insulin levels. IDE is involved in Alzheimer's disease, diabetes, and cardiovascular disease via oxidation and nitrosylation of IDE in oxidative stress. Reduced IDE activity, e.g. due to genetic dysfunction, leads to hyperinsulinemia and type 2 diabetes mellitus
physiological function
-
IDE is involved in amyloid beta degradation. Cerebral accumulation of amyloid beta protein is believed to play a central role in the pathogenesis of Alzheimer's disease. Therefore the gene encoding for insulin degrading enzyme is one of the candidate genes risky for Alzheimer's disease
physiological function
-
IDE is involved in the clearance of many bioactive peptide substrates, including insulin and amyloid-beta, peptides vital to the development of diabetes and Alzheimer's disease, respectively. IDE can also rapidly degrade hormones that are held together by intramolecular disulfide bond(s) without their reduction. Furthermore, IDE exhibits a remarkable ability to preferentially degrade structurally similar peptides such as the selective degradation of insulin-like growth factor-II and transforming growth factor-alpha, TGF-alpha, over IGF-I and epidermal growth factor, respectively
physiological function
-
IDE plays a key role in degrading both amyloid beta and insulin
physiological function
-
IDE plays a key role in degrading both amyloid beta and insulin
physiological function
-
IDE plays a primary role in insulin degradation and cellular insulin processing
physiological function
-
responsible for in vivo degradation of insulin, amyloid beta, and other peptide hormones, e.g. of insulin-like peptide 3, INSL3, an insulin superfamily peptide hormone, primarily expressed in the testes and playing a key role in the fetus testes descent and suppression of male germ cell apoptosis
physiological function
-
reducing expression levels of IDE profoundly alters the response of natriuretic peptide receptors (NPR-A and NPR-B) to the stimulation of ANP, BNP, and CNP in cultured cells. IDE rapidly cleaves ANP and CNP, thus inactivating their ability to raise intracellular cGMP. Reduced IDE expression enhances the stimulation of NPR-A and NPR-B by ANP and CNP, respectively. IDE cleavage can lead to hyperactivation of BNP toward NPR-A. Conversely, decreasing IDE expression reduces BNP-mediated signaling
physiological function
beta-site amyloid precursor protein-cleaving enzyme BACE2 overexpression in cultured cells lowers net amyloid beta levels with comparable effectiveness to insulin degrading enzyme
physiological function
insulin-degrading enzyme selectively degrades the monomer of amyloidogenic peptides and contributes to clearance of amyloid-beta. Thus, the enzyme retards the progression of Alzheimers disease
physiological function
the enzyme provokes growth reduction mediated by the phosphatidylinositol-3-phosphate kinase pathway in a cell-autonomous manner
physiological function
INS20-19 is involved in the invasion or early developmental process of Cryptosporidium parvum
physiological function
role of insulin-degrading enzyme in the intracytosolic clearance of amyloid beta and other amyloid-like peptides
physiological function
the enzyme has a minimal role in insulin metabolism in vivo. It may be more important in helping regulate amylin clearance
physiological function
the enzyme is implicated in proteolysis of insulin
physiological function
the enzyme is involved in pathways that modulate short-term glucose homeostasis
physiological function
the enzyme plays a critical role in both the proteolytic degradation and inactivation of insulin
additional information
-
IDE activity protects against Alzheimer's disease, IDE suppression of IDE induces the pathology
additional information
-
IDE can be intricately regulated by reactive oxygen or nitrogen species, identification of oxidation and nitrosylation sites, structure of IDE, and molecular basis for the long distance interactions, and mechanism of oxidative and nitrosylative modification of IDE, overview
additional information
-
interplay between retinoblastoma tumor suppressor protein and IDE within the proteasome that may have important growth-regulatory consequences
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A140D
specific activity with the substrates (7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH and (7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH is below 1 nmol/min*mg
A140F
specific activity with the substrates (7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH and (7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH is below 1 nmol/min*mg
A140K
specific activity with the substrates (7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH and (7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH is below 1 nmol/min*mg
A140N
specific activity with the substrates (7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH and (7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH is below 1 nmol/min*mg
A140W
specific activity with the substrates (7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH and (7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH is below 1 nmol/min*mg
A140Y
specific activity with the substrates (7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH and (7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH is below 1 nmol/min*mg
C819A
-
thiol-directed modification of C819 likely causes local structure perturbation to reduce substrate binding and catalysis
D426A
mutation diminishes activity
E107Q
catalytically inactive mutant
E110Q
-
structure comparison to wild-type enzyme structure
E111F
-
a mixed dimer in which one subunit contains the wild-type sequence and the other contains a E111F mutation that permits substrate binding, but not catalysis (E111F), exhibits a decrease in turnover number. A mixed dimer consisting of IDE:mutant E111F/Y609F IDE shows a high reduction in kcat, Km (Abz-GGFLRKHGQ-EDDnp) is 66% reduced compared to wild-type. Mixed dimer IDE:mutant E111F in which the inactive subunit can bind substrate exhibites a decreased activity than wild-type IDE towards substrate amyloid beta peptide
E341A
-
mutant is active in degrading substrate V, relative activity closed to wild-type
E341K
-
mutant is active in degrading substrate V, relative activity 15% compared to wild-type. Exosite mutant is unable to further degrade the Ub1-74 fragment
E341Q
-
mutant is active in degrading substrate V, relative activity 20% compared to wild-type. Exosite mutant is unable to further degrade the Ub1-74 fragment
F530A
the mutation renders the enzyme hyperactive, with up to a 20fold enhancement in degrading activity
F807A
mutation decreass the Km-value of the amyloid beta substrate
G339P
-
mutant is active in degrading substrate V, relative activity 75% compared to wild-type. Exosite mutant is unable to further degrade the Ub1-74 fragment
G361A/G362A
the mutant has reduced enzymatic activity
G361P
-
mutant is active in degrading substrate V, relative activity 80% compared to wild-type. Exosite mutant is unable to further degrade the Ub1-74 fragment
H112Q
-
a mixed dimer composed of one wild-type subunit and the other subunit containing a H112Q mutation that neither permits substrate binding nor catalysis exhibits the same turnover number per active subunit as wild-type IDE. Mixed oligomer IDE:IDE mutant H112Q shows similar kcat and Km (Abz-GGFLRKHGQ-EDDnp) compared to wild-type. Mixed dimer IDE:mutant H112Q IDE in which the inactive subunit does not bind substrate exhibits a slightly higher activity than wild-type IDE towards substrate amyloid beta peptide
K364A
mutation does not change the activity
N184C/Q828C
-
30-40fold increase in activity compared to wild-type
P284G
the mutation results in a slight reduction of enzyme catalysis
P286G
the mutation results in a significant reduction of enzyme catalysis
P289G
the mutant shows wild type activity
P292G
the mutation results in intermediate reduction of enzyme catalysis
R183a
about 35% of the activity compared to wild-type enzyme with the substrate
R183D
less than 5% of the activity compared to wild-type enzyme with the substrate (7-methoxycoumarin-4-yl)acetyl-KLVFFAEDK(Dnp)-OH
R183E
about less than 5% of the activity compared to wild-type enzyme with the substrate (7-methoxycoumarin-4-yl)acetyl-KLVFFAEDK(Dnp)-OH
R183K
about 30% of the activity compared to wild-type enzyme with the substrate (7-methoxycoumarin-4-yl)acetyl-KLVFFAEDK(Dnp)-OH
R183N
about 10% of the activity compared to wild-type enzyme with the substrate (7-methoxycoumarin-4-yl)acetyl-KLVFFAEDK(Dnp)-OH
R183Q
mutant Pitrm1 R183Q is implicated in inherited amyloidogenic neuropathy. Recombinant R183Q mutant is less active than the recombinant wild-type enzyme against recombinant amyloid beta-peptide (Abeta1-40). R183Q mutant enzyme exhibits significantly decreased rate of fluorogenic peptide hydrolysis ((7-methoxycoumarin-4-yl)acetyl-KLVFFAEDK(Dnp)-OH), yet retains similar binding affinity by comparison with the wild-type enzyme. Residue R183 is positioned within an N-terminal strand-loop-strand motif that is essential for enzyme function. A requirement for charged residues within 4.5 A of residue R183 is demonstrated. The R183Q mutant enzyme exhibits increased sensitivity to heat inactivation
R767A
the mutant exists mostly as a monomer
S137A
mutation decreass the Km-value of the amyloid beta substrate
Y496A
the mutation dramatically impairs the enzymatic activity
Y609F
-
mutation Y609F in the distal part of the substrate binding site of the active subunit blocks allosteric activation regardless of the activity of the other subunit. A mixed dimer consisting of mutant Y609F IDE: mutant E111F IDE shows a high reduction in kcat and a reduction in Km compared to wild-type. A mixed dimer consisting of mutant Y609F IDE: mutant E111F/Y609F IDE shows a high reduction in kcat, Km (Abz-GGFLRKHGQ-EDDnp) is 50% reduced compared to wild-type. Substrate amyloid beta peptide: When the distal site is mutated on both subunits (Y609F IDE:IDE Y609F) there is an even greater decrease in the reaction rate
Y831A
specific activity with the substrates (7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH and (7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH is below 1 nmol/min*mg
Y831D
specific activity with the substrates (7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH and (7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH is below 1 nmol/min*mg
Y831K
specific activity with the substrates (7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH and (7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH is below 1 nmol/min*mg
Y831N
specific activity with the substrates (7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH and (7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH is below 1 nmol/min*mg
Y831W
specific activity with the substrates (7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH and (7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH is below 1 nmol/min*mg
E111A
-
change in the substrate response from sigmoidal to hyperbolic. Activating effect of ATP or triphosphate with substrate 2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine) on wild-type is dampened. Mutant recognizes additional cleavage sites in substrate beta-endorphin
E111L
-
change in the substrate response from sigmoidal to hyperbolic. Activating effect of ATP or triphosphate with substrate 2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine) on wild-type is dampened. Mutant recognizes additional cleavage sites in substrate beta-endorphin
E111V
-
change in the substrate response from sigmoidal to hyperbolic. Activating effect of ATP or triphosphate with substrate 2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine) on wild-type is dampened. Mutant recognizes additional cleavage sites in substrate beta-endorphin
E768A
-
naturally occuring mutation of IDE
H112D
-
change in the substrate response from sigmoidal to hyperbolic. Activating effect of ATP or triphosphate with substrate 2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine) on wild-type is changed to inhibition. Affinity to Zn2+ is lower than in wild-type
H112Q
-
change in the substrate response from sigmoidal to hyperbolic. Activating effect of ATP or triphosphate with substrate 2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine) on wild-type is changed to inhibition. Affinity to Zn2+ is lower than in wild-type
I374S
-
mutation in the distal site eliminates allosterism, Vmax decreased approximately 10fold compared to wild-type, Km (Abz-GGFLRKHGQ-EDDnp) roughly similar to wild-type, no heterotropic activation with bradykinin, no significant activation through ATP
R429S
-
mutant shows greatly decreased activation by the polyphosphate anions ATP and PPP. kcat (Abz-GGFLRKHGQ-EDDnp) comparable to wild-type and Km (Abz-GGFLRKHGQ-EDDnp) higher than wild-type
V360S
-
mutation in the distal site eliminates allosterism, Vmax decreased approximately 10fold compared to wild-type, Km (Abz-GGFLRKHGQ-EDDnp) roughly similar to wild-type, no heterotropic activation with bradykinin, ATP activation is reduced to 8fold
Y248C
-
naturally occuring mutation of IDE
D426C/K899C
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30-40fold increase in activity compared to wild-type
D426C/K899C
site-directed mutagenesis, hyperactive IDE mutation, the mutant shows increased activity, but reduced activationby ATP compared to the wild-type enzyme
E111Q
-
catalytically inactive mutant
E111Q
-
crystallization data
E111Q
site-directed mutagenesis, inactive mutant
E111Q
inactive enzyme form
E111Q
-
site-directed mutagenesis, the mtant shows highly reduced catalytic activity compared to the wild-typ enzyme
E111Q
-
catalysitcally inactive. Mutant forms ordered crystals of considerable size at a more rapid rate than the wild type
E111Q
specific activity with the substrates (7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH and (7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH is below 1 nmol/min*mg
K898A
mutation decreass the Km-value of the amyloid beta substrate
K898A
mutation results in increased catalytic activity
S132C/E817C
-
30-40fold increase in activity compared to wild-type
S132C/E817C
the mutant preferentially stays in the closed state
Y831F
site-directed mutagenesis, the mutant shows catalytic activity similar to the wild-type enzyme
Y831F
specific activity with the substrates (7-methoxycoumarin-4-yl)acetyl-VEALYLVCGEK(2,4-dinitrophenyl)-OH and (7-methoxycoumarin-4-yl)acetyl-QKLVFFAEDVK(2,4-dinitrophenyl)-OH is below 1 nmol/min*mg
E111F
-
change in the substrate response from sigmoidal to hyperbolic. Activating effect of ATP or triphosphate with substrate 2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine) on wild-type is dampened. Mutant recognizes additional cleavage sites in substrate beta-endorphin
E111F
-
crystal structure of a catalytically compromised E111F mutant of IDE has electron density for peptide ligands bound at the active site in domain 1 and a distal site in domain 2
H18R/A890V
plus silent mutation at codon 934, naturally occuring missense mutations occuring in a rat model of type 2 diabetes mellitus, resulting in decreased catalytic efficiency and 15-30% deficit in degradation of both insulin and insulin Abeta. Endogenously secreted insulin Abeta40 and Abeta42 are significantly elevated in primnary neuronal cultures from mutant animals
H18R/A890V
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naturally occuring mutations in the insulysin gene in GK rats causing 30% reduced enzyme activity and type 2 diabetes as well as increased amyloid beta peptide levels , the rats exhibit defects in both insulin action and insulin degradation, the increased amyloid beta-peptide levels do not lead to increased steady-state levels of its activity due to compensatory degradative mechanisms in the brain
K898A/K899A/S901A
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mutant shows greatly decreased activation by the polyphosphate anions ATP and PPP, mutant is also deficient in activation by small peptides and has reduced intracellular function relative to unmodified IDE. Km and kcat (Abz-GGFLRKHGQ-EDDnp) higher than wild-type
K898A/K899A/S901A
variant with mutations in the polyanion-binding site shows reduced activation by myoinositol 1,4,5-trisphosphate and phytic acid
Y609F
-
mutation in the distal site eliminates allosterism, Vmax decreased approximately 10fold compared to wild-type, Km (Abz-GGFLRKHGQ-EDDnp) roughly similar to wild-type, no heterotropic activation with bradykinin, no significant activation through ATP
Y609F
activation by myoinositol 1,4,5-trisphosphate and phytic acid is decreased in the mutant enzyme
additional information
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chromosome 10-linked Alzheimer disease families show decreased enzyme activity
additional information
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construction of transgenic mice, termed H1/siRNAinsulin-CMV/hIDE transgenic mice, TG9385, co-expressing specific insulin siRNA sequences and the human insulin degrading enzyme, hIDE, gene resulting in changes in the proteins in the endoplasmic reticulum stress signal pathway and a diabetes-like phenotype with impaired glucose tolerance and lower serum insulin levels compared to the wild-type mice, expression pattern in muscle, lung, brain, liver, kidney, heart, and intestine, tissue-specific regulation, overview
additional information
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enzyme deficiency leads to development of either Alzheimer's disease and type 2 diabetes, overview
additional information
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genotyping of single nucleotide polymorphisms in the IDE gene in Finnish patients with Alzheimer's disease, SNPs rs4646953 and rs4646955 to be associated with Alzheimer's disease, the insulin-degrading enzyme is genetically associated with Alzheimer's disease in the Finnish population, overview
additional information
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human enzyme co-expression with specific insulin siRNA in H1/siRNAinsulin-CMV/hIDE transgenic mice, TG9385, using a chromosome integrated dual-recombinant expression system, in lung, brain, liver, kidney, heart, and intestine, with significantly increased enzyme level and activity in the liver, the transgenic mice show impaired glucose tolerance and reduced serum insulin levels compared to wild-type mice, down-regulation of gene transcripts in the liver of H1/siRNAinsulin-CMV/hIDE mice, gene ontology, overview
additional information
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no correlation of single nucleotide polymorphisms and IDE haplotypes with the risk of dementia, overview
additional information
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overexpression of insulysin in human amyloid precursor protein transgenic mice leads to a decrease in amyloid beta peptide levels
additional information
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siRNA-mediated gene silencing of IDE in Hep-G2 cells leading to 50% reduction of IDE mRNA and protein, short-lived protein degradation is unchanged in the cells with reduced IDE expression, while long-lived and very-long-lived protein degradation is reduced, overview
additional information
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construction of mutants lacking one or severall cysteine resiudes. A mutant devoid of all 13 cysteine residues is insensitive to the inhibition by S-nitrosoglutathione, hydrogen peroxide, or N-ethylmaleimide
additional information
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construction of Cys residue mutants of IDE, properties of oxidized and/or nitrosylated mutant enzymes compared to wild-type enzyme, overview
additional information
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IDE genotyping and identification of genetic variants, the A/T allele of IDE gene variant rs11187033 is associated with the metabolic syndrome, and might contribute to metabolic syndrome susceptibility in Chinese elders, overview
additional information
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IDE genotyping identification of polymorphisms, three polymorphisms occur in IDE promoter: -1002T/G (rs3758505), -179T/C (rs4646953) and -51C/T (rs4646954). The -1002T and -51C alleles are overrepresented in 357 sporadic Alzheimer disease patients when compared to those in 331 healthy individuals. Furthermore, -1002T/G and -51C/T are in strong linkage disequilibrium and they construct a relatively risky -1002T/-51C and a relatively protective -1002G/-51T
additional information
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identification of a genetic variant 311 rs6583817, found in two Croatian isolated populations, unequivocally associated with increased IDE expression that is also associated with reduced plasma amyloidbeta40 and decreased late onset Alzheimer's disease susceptibility. rs6583817 increases reporter gene expression in Be(2)-C and Hep-G2 cell lines. Additional eleven IDE haplotypes, that also show significant association, overview
additional information
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silencing of IDE in Hep-Ge cells by siRNA inhibits insulin degradation by up to 76%
additional information
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Tg3576 transgenic mice express the Swedish mutant of amyloid beta-peptide, the expression and activity of IDE in the transgenic mice is increased with age around plaques as a component of astrocyte activation due to amyloid beta-peptide-triggered inflammation in contrast to the behaviour in Alzheimer mice, overview
additional information
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IDE knockout mice show decreased insulin degradation and associated hyperinsulinemia
additional information
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heterologous expression in Saccharomyces cerevisiae, enzyme can promote the in vivo production of yeast a-factor mating pheromone, but cannot substitue for other fuctions of yeast Axl1p. Enzyme requires an intact C-terminus for optimal activity
additional information
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construction of transgenic mice with increased enzyme levels show that the enzyme prevents and treats Alzheimer's disease formation
additional information
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mutant with a deleted putative dimer interface in the C-terminal region is created, which results in a monomeric variant. Monomeric IDE retains enzymatic activity. Monomeric IDE retains, 25% of the wild type activity substrate (Abz-GGFLRKHGQ-EDDnp). With the peptide substrates beta-endorphin and amyloid beta peptide 1-40, monomeric IDE retains 1 to 0.25% of wild type activity. No activation through bradykinin or dynorphin B-9. Monomeric IDE is not activated by polyphosphates
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