Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
2',3'-dialdehyde-ATP
-
i.e. adenosine 2',3'-dialdehyde triphosphate, in the presence of ATP, globin as substrate
3,4-dichloroisocoumarin
-
-
Acetyl-Gly-Gly-Ala chloromethyl ketone
-
-
adenosine 5'-(3-thiotriphosphate)
-
i.e. ATP-gamma-S, in the presence of ATP, globin as substrate
Adenosine 5'-(betathio)triphosphate
-
-
adenosine 5'-[beta,gamma-imido]triphosphate
-
protein and ATP hydrolysis
adenyl-5'-yl methylene diphosphonate
-
i.e. AMP-PCP
Ala-Lys-Arg chloromethyl ketone
-
weak, casein as substrate
alpha,beta-methylene-ATP
-
in the presence of ATP, globin as substrate
anti-sense morpholino oligonucleotide
-
causes defects in mitochondrial membrane potential, respiration and morphology, as well as apoptotic cell death
-
bacteriophage T4 PinA protein
-
Bacteriophage T4 protease inhibitor PinA
-
-
-
Benzoyl-Arg-Gly-Phe-methoxynaphthylamide
-
-
Benzoyl-Arg-Gly-Phe-Phe-Leu-methoxynaphthylamide
-
glutaryl-Ala-Ala-Phe-methoxynaphthylamide or casein as substrate
benzyloxycarbonyl-Gly-Leu-Phe chloromethyl ketone
benzyloxycarbonyl-Gly-Leu-Pro chloromethyl ketone
-
-
Benzyloxycarbonyl-Gly-NH-C6H4SO2-Phe
-
weak
benzyloxycarbonyl-Phe chloromethyl ketone
cardiolipin
-
cardiolipin-containing liposomes specifically inhibit both the proteolytic and ATPase activities of Lon in a dose-dependent manner. Cardiolipin-containing liposomes selectively bind to Lon. The interaction between cardiolipin-containing liposomes and Lon changes with the order of addition of Mg2+/ATP. When cardiolipin-containing liposomes are added after the addition of Mg2+/ATP to Lon, the binding of cardiolipin-containing liposomes to Lon is significantly decreased as compared with the reversed order
Cb2-Leu-Leu-Leu-aldehyde
-
-
clasto-lactacystin beta-lactone
Dansyl fluoride
-
protein and ATP hydrolysis
dansyl-YRGIT-Abu
-
not time-dependent inhibitor of peptide hydrolysis activity of lon
Denatured lambda Cro protein
-
casein as substrate
-
diisopropyl fluorophosphate
dimethylformamide
-
above 5%
Dimethylsulfoxide
-
above 5%
Dio-9
-
ATPase inhibitor
-
ethylenediaminetetraacetic acid
-
-
Glutaryl-Ala-Ala-Phe
-
ATP hydrolysis
Glutaryl-Ala-Ala-Phe-methoxynaphthylamide
H2O2
-
blocks enzymatic activity but has no appreciable effect on sequence-specific binding to DNA. 0.1 mM decreases proteolytic activity to ca. 60%, at 0.5, 1, and 4 mM protease activity is reduced to 18, 9, and 5%, respectively
isopropylboronic acid
-
-
lambda-N-Protein
-
casein as substrate
-
Mersalyl acid
-
strong, 5 mM, casein as substrate
MG 262
-
is a potent peptide-based inhibitor
Mg2+
excess of magnesium ions has an inhibitory effect on the hydrolysis of ATP
N,N'-dicyclohexylcarbodiimide
p-nitroanthranilate
-
weak
Peptide substrates
-
inhibit ATP hydrolysis, protein substrates promote ATP hydrolysis
-
peroxynitrite
-
in isolated nonsynaptic brain mitochondria Lon protease is highly susceptible to oxidative inactivation by peroxynitrite. This susceptibility is more pronounced with regard to ATP-stimulated activity, which is inhibited by 75% in the presence of a bolus addition of 1 mM ONOO, whereas basal unstimulated activity is inhibited by 45%. A decline in Lon protease activity precedes electron transport chain dysfunction and ATP-stimulated activity is approximately fivefold more sensitive than basal Lon protease activity. Supplementation of mitochondrial matrix extracts with reduced glutathione, following peroxynitrite exposure, results in partial restoration of basal and ATP-stimulated activity
phenylmethylsulfonyl fluoride
Protein R9 from Escherichia coli mutant strain capR9
-
protein, peptide and ATP hydrolysis
-
Succinyl-Phe-Ala-Phe-methoxynaphthylamide
-
ATP hydrolysis
TorD
-
impairs the enzyme's TorA degradation activity by binding to apoTorA
-
tosyl-Lys chloromethyl ketone
tosyl-Phe chloromethyl ketone
ADP
-
protein and ATP hydrolysis
ADP
-
prevents activation by ATP
ADP
-
prevents activation by ATP; strong
ADP
-
prevents activation by ATP; prevents activation by diphosphate
ADP
-
ADP-binding in the presence of EDTA; kinetics; product inhibition
ADP
-
ADP-release is rate-limiting step; binds 4 mol ADP per enzyme tetramer
ADP
-
inhibits proteolytic activity of lon
ADP
non-competitive inhibition, ELon binds to ADP and undergoes at least one structural change that exposes a tryptic digestion site
ADP
free ADP inhibits all forms of Ec-Lon, while a complex of ADP with magnesium ions (ADP-Mg) activates C-His-Lon and Lon-R164A and inhibits the mutant forms Lon R192A and Lon-Y294A
ADP
non-competitive inhibition dependent on substrate concentration, steady-state ADP inhibition study, overview. hLon binds to ADP and undergoes at least one structural change that exposes a tryptic digestion site
ADP
moderate inhibition of 36%
ADP
-
wild-type, up to 60% inhibition, mutant K63A, slight activation, mutants D241A, N293A, R375A, about 50% inhibition of peptidase activity. Complete inhibition of hydrolysis of FITC
AMP
-
in the presence of ATP
ATP
-
-
ATP
-
inhibits binding of enzyme to DNA or RNA
ATP
-
inhibits DNA binding by lon
ATP
-
ATP-binding inhibits DNA binding
ATP
-
substrate inhibition of wild-type and mutant enzymes, kinetics, overview
ATP
-
peptidase activity of enzyme is modulated by the ATP-state of the AAA+ domain. Absence of nucleotide results in basal activity, presence of ATP reduces the basal activity. Presence of ATP stimulates hydrolysis of FITC 10fold
bacteriophage T4 PinA protein
-
inhibits degradation of alpha-methyl-casein and CcdA, noncompetitive inhibition, no inhibition of cleavage of N-glutaryl-alanylalanylphenylalanyl-3-methoxynaphthylamide
-
bacteriophage T4 PinA protein
-
specifically inhibits Escherichia coli Lon
-
benzyloxycarbonyl-Gly-Leu-Phe chloromethyl ketone
-
strong
benzyloxycarbonyl-Gly-Leu-Phe chloromethyl ketone
-
-
benzyloxycarbonyl-Phe chloromethyl ketone
-
weak
benzyloxycarbonyl-Phe chloromethyl ketone
-
-
beta,gamma-methylene-ATP
-
not
beta,gamma-methylene-ATP
-
in the presence of ATP, globin as substrate
bortezomib
-
-
bortezomib
enzyme-bound structure analysis
chymostatin
-
weak
chymostatin
-
not (casein as substrate)
clasto-lactacystin beta-lactone
-
blocks lon-mediated degradation of steroidogenic acute regulatory protein or FITC casein
clasto-lactacystin beta-lactone
-
-
dansyl-YRGIT-Abu-B(OH)2
-
i.e. DBN93, site-directed peptide inhibitor with two-step mechanism
dansyl-YRGIT-Abu-B(OH)2
-
potent time-dependent inhibitor of peptide hydrolysis activity of lon, inhibition requires the binding but not hydrolysis of ATP, is an alternative peptidyl boronate inhibitor
diisopropyl fluorophosphate
-
protein and ATP hydrolysis
diisopropyl fluorophosphate
-
-
diisopropyl fluorophosphate
-
E. coli
diisopropyl fluorophosphate
-
10 mM, casein as substrate
diisopropyl fluorophosphate
-
-
diisopropyl fluorophosphate
-
inhibition indicates that the enzyme is a serine protease
diisopropyl fluorophosphate
-
-
EDTA
-
casein as substrate; strong
Glutaryl-Ala-Ala-Phe-methoxynaphthylamide
-
weak, casein as substrate
Glutaryl-Ala-Ala-Phe-methoxynaphthylamide
-
ATP-hydrolysis
iodoacetamide
-
at high concentration, protein and ATP-hydrolysis
iodoacetamide
-
10 mM, casein as substrate
MG132
-
blocks lon-mediated degradation of steroidogenic acute regulatory protein or FITC casein
MG132
-
causes calpain 10 accumulation in vivo
MG262
-
-
MG262
-
most potent inhibitor, requires binding, but not hydrolysis, of ATP to initiate inhibition
MG262
-
potent time-dependent inhibitor of peptide hydrolysis activity of lon, inhibition requires the binding but not hydrolysis of ATP
MG262
-
i.e. Cb2-Leu-Leu-Leu-bornic acid
N,N'-dicyclohexylcarbodiimide
-
not
N,N'-dicyclohexylcarbodiimide
-
weak
N-ethylmaleimide
-
-
N-ethylmaleimide
-
not (casein as substrate)
N-ethylmaleimide
-
1 mM, strong; high sensitivity to N-ethylmaleimide (NEM) points to an essential role of sulfhydryl groups in the enzyme activity
N-ethylmaleimide
-
enzyme particularly sensitive to, pointing to an essential role of sulfllydryl groups in enzymatic activity
N-ethylmaleimide
-
the candidate for the NEM binding could be Cys406 located close to the ATP binding site (Gly409-Ser417) and highly conserved between Lon proteases
NaCl
-
at high concentrations
oligomycin
-
weak
phenylmethylsulfonyl fluoride
-
inhibition indicates that the enzyme is a serine protease
phenylmethylsulfonyl fluoride
-
-
PMSF
-
-
PMSF
-
1 mM, casein as substrate
PMSF
-
inhibition of the yeast enzyme activity by PMSF indicates that, the enzyme is also a serine protease
Polyphosphate
-
competitively blocks DNA binding by lon in vitro and in vivo
Polyphosphate
-
slightly inhibits degradation of a maltose-binding protein-SulA fusion. At the ATP domain competes with DNA for binding to lon, completely inhibits the formation of a DNA-lon complex
quercetin
-
-
RNAi
-
-
-
RNAi
-
lon depletion, cells show little if any mitochondrial DNA damage
-
RNAi
-
knockdown of lon
-
tosyl-Lys chloromethyl ketone
-
i.e. 1-chloro-3-tosylamido-2-heptanone; weak, casein as substrate, no inhibition with glutaryl-Ala-Ala-Phe methoxynaphthylamide as substrate
tosyl-Lys chloromethyl ketone
-
weak, casein as substrate, no inhibition with glutaryl-Ala-Ala-Phe methoxynaphthylamide as substrate
tosyl-Lys chloromethyl ketone
-
not (casein as substrate)
tosyl-Phe chloromethyl ketone
-
i.e. tosyl-2-phenylethyl chloromethyl ketone
tosyl-Phe chloromethyl ketone
-
-
tosyl-Phe chloromethyl ketone
-
not (casein as substrate)
vanadate
-
casein and ATP hydrolysis
vanadate
-
ATPase inhibitor; does not inhibit but even stimulates peptide hydrolysis; inhibits protein hydrolysis
vanadate
-
decavanadate (not orthovanadate)
vanadate
-
0.1 mM; casein as substrate
vanadate
-
activity of the yeast protease is sensitive to vanadate, a potent inhibitor of many ATPases
additional information
-
termination factor rho or NaN3
-
additional information
-
methoxynaphthylamide (ATP-hydrolysis)
-
additional information
-
casein (with peptides as substrates)
-
additional information
-
high-affinity site of lon can be blocked with unlabeled nucleotide, conformational change associated with nucleotide binding
-
additional information
-
inhibition of activity by the T4-encoded PinA protein, non-competetive inhibitor
-
additional information
-
lon protease expression and activity declines with age
-
additional information
-
expression of an inducible short hairpin RNA leading to lon depletion in a colon adenocarcinoma cell line for 14 days does not lead to cell death. Even after RNAi knockdown for 3 weeks, these cells continue to survive, although they no longer proliferate
-
additional information
-
not inhibited by epoxomicin
-
additional information
-
binding structure of inhibitors, substrate-binding groove with covalently bound inhibitors, two peptidomimetics and one derived from a natural product, structural basis of inhibitor recognition, overview
-
additional information
-
Lon protease expression and activity declines with age, steady-state levels of lon mRNA are ca. 4fold lower in 30-month-old mice than in young mice. 5fold decrease in protein levels and activity in old mice compared to young mice
-
additional information
-
no inhibition by ubiquitin, bestatin, soybean trypsin inhibitor, aprotinin, leupeptin
-
additional information
-
total activity of lon decreases about 2.5fold in old liver, protein level does not change in old compared to young liver
-
additional information
-
epoxomicin, ZL3-VS and ethylboronic acid are ineffective at inhibiting lon at micromolar concentrations
-
additional information
-
inhibitory profile corresponds to those of ATP-dependent serine proteases of Lon (La) family. Properties compared with ATP-dependent proteases from different sources
-