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Literature summary for 3.4.24.56 extracted from

  • Guo, Q.; Manolopoulou, M.; Bian, Y.; Schilling, A.B.; Tang, W.J.
    Molecular basis for the recognition and cleavages of IGF-II, TGF-alpha, and amylin by human insulin-degrading enzyme (2010), J. Mol. Biol., 395, 430-443.
    View publication on PubMedView publication on EuropePMC

Crystallization (Commentary)

Crystallization (Comment) Organism
X-ray diffraction structure determination and analysis of enzyme-substrate complexes IDE-IGF-II and IDE-TGF-alpha at 2.3 A resolution and IDE-amylin at 2.9 A resolution Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
amylin + H2O Homo sapiens 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 amylin peptide fragments
-
?
amyloid beta + H2O Homo sapiens
-
amyloid beta peptide fragments
-
?
epidermal growth factor + H2O Homo sapiens identification of cleavage sites by mass spectrometry and NMR epidermal growth factor peptide fragments
-
?
insulin + H2O Homo sapiens
-
insulin peptide fragments
-
?
insulin-like growth factor-II + H2O Homo sapiens identification of cleavage sites by mass spectrometry and NMR insulin-like growth factor-II peptide fragments
-
?
additional information Homo sapiens 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 ?
-
?
reduced amylin + H2O Homo sapiens identification of cleavage sites by mass spectrometry reduced amylin peptide fragments
-
?
transforming growth factor-alpha + H2O Homo sapiens identification of cleavage sites by mass spectrometry transforming growth factor-alpha peptide fragments
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Reaction

Reaction Comment Organism Reaction ID
Degradation of insulin, glucagon and other polypeptides. No action on proteins ability of substrates to properly anchor their N-terminus to the exosite of IDE and undergo a conformational switch upon binding to the catalytic chamber of IDE can also contribute to the selective degradation of structurally related growth factors. The high dipole moment of substrates complements the charge distribution of the IDE catalytic chamber for the substrate selectivity Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
amylin + H2O 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 Homo sapiens amylin peptide fragments
-
?
amyloid beta + H2O
-
Homo sapiens amyloid beta peptide fragments
-
?
epidermal growth factor + H2O identification of cleavage sites by mass spectrometry and NMR Homo sapiens epidermal growth factor peptide fragments
-
?
insulin + H2O
-
Homo sapiens insulin peptide fragments
-
?
insulin-like growth factor-II + H2O identification of cleavage sites by mass spectrometry and NMR Homo sapiens insulin-like growth factor-II peptide fragments
-
?
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 Homo sapiens ?
-
?
reduced amylin + H2O identification of cleavage sites by mass spectrometry Homo sapiens reduced amylin peptide fragments
-
?
transforming growth factor-alpha + H2O identification of cleavage sites by mass spectrometry Homo sapiens transforming growth factor-alpha peptide fragments
-
?

Synonyms

Synonyms Comment Organism
IDE
-
Homo sapiens
Insulin-degrading enzyme
-
Homo sapiens

General Information

General Information Comment Organism
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 Homo sapiens