Information on EC 3.4.24.56 - insulysin

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The expected taxonomic range for this enzyme is: Coelomata

EC NUMBER
COMMENTARY hide
3.4.24.56
-
RECOMMENDED NAME
GeneOntology No.
insulysin
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
Degradation of insulin, glucagon and other polypeptides. No action on proteins
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY hide
9013-83-6
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
Frog
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Wistar strain
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(7-methoxycoumarin-4-yl)acetyl-NPPGFSAFK-2,4-dinitrophenyl + H2O
?
show the reaction diagram
-
bradykinin mimetic substrate V
-
-
?
(7-methoxycoumarin-4-yl)acetyl-RPPGFSAFK-2,4-dinitrophenyl + H2O
?
show the reaction diagram
2-amino-benzoyl-GGFLRKAGQ-ethylenediamine-2,4-dinitrophenyl + H2O
?
show the reaction diagram
-
-
-
?
2-amino-benzoyl-GGFLRKHGQ-ethylenediamine-2,4-dinitrophenyl + H2O
?
show the reaction diagram
-
-
-
?
2-amino-benzoyl-GGFLRKMGQ-ethylenediamine-2,4-dinitrophenyl + H2O
?
show the reaction diagram
-
-
-
?
2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine) + H2O
?
show the reaction diagram
2-aminobenzoyl-GGFLRKHGQ-ethylenediamine-2,4-dinitrophenyl + H2O
2-aminobenzoyl-GGFLR + KHGQ-ethylenediamine-2,4-dinitrophenyl
show the reaction diagram
-
-
-
-
?
7-methoxycoumarin-4-yl-acetyl-RPPGF-SAFK-2,4-dinitrophenyl + H2O
?
show the reaction diagram
-
-
-
-
?
7-methoxycoumarin-4-yl-acetyl-RPPGFSAFK-2,4-dinitrophenyl + H2O
?
show the reaction diagram
-
fluorogenic bradykinin-mimetic IDE substrate V
-
-
?
7-methoxycoumarin-4-ylacetyl-NPPGFSAFK-2,4-dinitrophenyl + H2O
?
show the reaction diagram
-
-
-
-
?
Abz-GFLRKGVQ-EDDnp + H2O
?
show the reaction diagram
-
-
-
-
?
Abz-GGFLRKHGQ-EDDnp + H2O
Abz-GGFLR + KHGQ-EDDnp
show the reaction diagram
Abz-GGFLRKHGQEDDnp + H2O
Abz-GGFLRKHGQ + EDDnp
show the reaction diagram
-
synthetic fluorogenic substrate
-
-
?
Abz-SEKKDNYIIKGV-nitroY-OH + H2O
?
show the reaction diagram
-
a substrate based on the polypeptide sequence of the yeast P2 a-factor mating propheromone
-
-
?
amylin + H2O
?
show the reaction diagram
amylin + H2O
amylin peptide fragments
show the reaction diagram
amyloid alpha-peptide + H2O
?
show the reaction diagram
-
-
-
-
?
amyloid beta + H2O
amyloid beta peptide fragments
show the reaction diagram
amyloid beta peptide + H2O
?
show the reaction diagram
amyloid beta peptide 1-40 + H2O
?
show the reaction diagram
-
physiolgical substrate
-
?
amyloid beta-peptide + H2O
?
show the reaction diagram
amyloid beta-peptide 1-40 + H2O
?
show the reaction diagram
amyloid beta-peptide 1-42 + H2O
?
show the reaction diagram
-
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-peptide1-40 + H2O
?
show the reaction diagram
degradation
-
-
?
amyloid beta-protein + H2O
?
show the reaction diagram
amyloid beta-protein A21G + H2O
?
show the reaction diagram
-
Flemish genetic variant
-
-
?
amyloid beta-protein E22K + H2O
?
show the reaction diagram
-
Italian genetic variant
-
-
?
amyloid beta-protein E22Q + H2O
?
show the reaction diagram
-
Dutch genetic variant
-
-
?
amyloid beta1-40 + H2O
?
show the reaction diagram
-
-
-
-
?
amyloid beta40 + H2O
amyloid beta40 peptide fragments
show the reaction diagram
amyloid beta42 + H2O
amyloid beta42 peptide fragments
show the reaction diagram
amyloid peptide + H2O
?
show the reaction diagram
-
23 amino acid peptide resulting from internal proteolysis of wild-type type 2 transmembrane protein BRI2
-
-
?
amyloid peptide ABri + H2O
?
show the reaction diagram
-
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
?
show the reaction diagram
-
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
?
show the reaction diagram
ATP + H2O
ADP + phosphate
show the reaction diagram
Atrial natriuretic factor + H2O
?
show the reaction diagram
atrial natriuretic peptide + H2O
?
show the reaction diagram
-
-
-
?
ATTO 655-Cys-Lys-Leu-Val-Phe-Phe-Ala-Glu-Asp-Trp + H2O
?
show the reaction diagram
-
-
-
-
?
beta-amyloid peptide + H2O
?
show the reaction diagram
-
-
-
?
beta-amyloid precursor protein intracellular domain + H2O
?
show the reaction diagram
-
-
-
?
beta-amyloid protein + H2O
?
show the reaction diagram
beta-endorphin + H2O
?
show the reaction diagram
beta-endorphin + H2O
gamma-endorphin + ?
show the reaction diagram
Bradykinin + H2O
?
show the reaction diagram
calcitonin + H2O
?
show the reaction diagram
-
-
-
?
CH3NH-Ala-Ala-Ala-CONHCH3 + H2O
?
show the reaction diagram
-
energetic profile of proteolysis mechanism of IDE
-
-
?
CH3NH-Leu-Tyr-Leu-CONHCH3 + H2O
?
show the reaction diagram
-
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
?
show the reaction diagram
-
fluorogenic derivative of amyloid beta containing residues 10-25
-
-
?
dynorphin A-17 + H2O
?
show the reaction diagram
-
-
-
?
dynorphin B-13 + H2O
?
show the reaction diagram
-
-
-
?
dynorphin B-9 + H2O
?
show the reaction diagram
-
-
-
?
epidermal growth factor + H2O
epidermal growth factor peptide fragments
show the reaction diagram
-
identification of cleavage sites by mass spectrometry and NMR
-
-
?
Fragment of cytochrome c + H2O
Hydrolyzed fragment of cytochrome c
show the reaction diagram
-
Ile81-Glu108
cleavage at Tyr97-Leu98 bond
-
Glucagon + H2O
?
show the reaction diagram
glucagon + H2O
glucagon peptide fragments
show the reaction diagram
-
-
-
-
?
Glucagon + H2O
Hydrolyzed glucagon
show the reaction diagram
haemoglobin + H2O
?
show the reaction diagram
-
damaged haemoglobin oxidatively degraded
-
?
InsL3 + H2O
InsL3 fragments
show the reaction diagram
insulin + H2O
?
show the reaction diagram
Insulin + H2O
Hydrolyzed insulin
show the reaction diagram
insulin + H2O
insulin fragments
show the reaction diagram
insulin + H2O
insulin peptide fragments
show the reaction diagram
Insulin B-chain + H2O
?
show the reaction diagram
Insulin growth factor II + H2O
?
show the reaction diagram
insulin-like growth factor I + H2O
insulin-like growth factor I peptide fragments
show the reaction diagram
insulin-like growth factor II + H2O
insulin-like growth factor II peptide fragments
show the reaction diagram
insulin-like growth factor-II + H2O
insulin-like growth factor-II peptide fragments
show the reaction diagram
-
identification of cleavage sites by mass spectrometry and NMR
-
-
?
insulin-like peptide 3 + H2O
processed insulin-like peptide 3 + WSTEA
show the reaction diagram
kallidin + H2O
?
show the reaction diagram
-
cleavage at Pro/Phe site
-
-
?
Lysozyme + H2O
?
show the reaction diagram
-
degradation of oxidatively damaged lysozyme
-
?
o-aminobenzoic acid-GGFLRKHGQ-ethylenediamine-2,4-dinitrophenyl + H2O
?
show the reaction diagram
-
-
-
?
Oxidatively damaged hemoglobin + H2O
?
show the reaction diagram
peptide containing the mitochondrial targeting sequence of E1alpha subunit of human pyruvate dehydrogenase + H2O
?
show the reaction diagram
-
hydrolysis occurs at several sites
-
-
?
peptide V + H2O
?
show the reaction diagram
Porcine proinsulin intermediates + H2O
?
show the reaction diagram
-
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
show the reaction diagram
-
15fold greater rate of insulin destruction over that for proinsulin
-
-
-
protein ANP + H2O
?
show the reaction diagram
-
-
-
-
?
protein BNP + H2O
?
show the reaction diagram
-
-
-
-
?
protein CNP + H2O
?
show the reaction diagram
-
-
-
-
?
protein DNP + H2O
?
show the reaction diagram
-
-
-
-
?
reduced amylin + H2O
reduced amylin peptide fragments
show the reaction diagram
-
identification of cleavage sites by mass spectrometry
-
-
?
relaxin + H2O
relaxin fragments
show the reaction diagram
relaxin-3 + H2O
relaxin-3 fragments
show the reaction diagram
somatostatin + H2O
?
show the reaction diagram
-
cleavage at Phe6-Phe7 bond
-
-
?
Transforming growth factor + H2O
?
show the reaction diagram
transforming growth factor alpha + H2O
?
show the reaction diagram
-
-
-
?
transforming growth factor-alpha + H2O
transforming growth factor-alpha peptide fragments
show the reaction diagram
-
identification of cleavage sites by mass spectrometry
-
-
?
Tryptic fragment of bovine serum albumin + H2O
Hydrolyzed tryptic fragment of bovine serum albumin
show the reaction diagram
-
Leu503-Lys518
cleaved at Phe506-His507
-
ubiquitin + H2O
?
show the reaction diagram
-
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
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
amylin + H2O
?
show the reaction diagram
amylin + H2O
amylin peptide fragments
show the reaction diagram
amyloid alpha-peptide + H2O
?
show the reaction diagram
-
-
-
-
?
amyloid beta + H2O
amyloid beta peptide fragments
show the reaction diagram
amyloid beta peptide 1-40 + H2O
?
show the reaction diagram
-
physiolgical substrate
-
?
amyloid beta-peptide + H2O
?
show the reaction diagram
amyloid beta-peptide 1-40 + H2O
?
show the reaction diagram
-
-
-
-
?
amyloid beta40 + H2O
amyloid beta40 peptide fragments
show the reaction diagram
amyloid beta42 + H2O
amyloid beta42 peptide fragments
show the reaction diagram
-
Abeta42, an Alzheimer amyloid beta peptide
-
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
insulin-binding and degradation are dependent on ATP concentration, however, insulin does not modify the ATPase activity of IDE
-
-
?
beta-endorphin + H2O
?
show the reaction diagram
-
-
-
-
?
beta-endorphin + H2O
gamma-endorphin + ?
show the reaction diagram
epidermal growth factor + H2O
epidermal growth factor peptide fragments
show the reaction diagram
-
identification of cleavage sites by mass spectrometry and NMR
-
-
?
Glucagon + H2O
?
show the reaction diagram
glucagon + H2O
glucagon peptide fragments
show the reaction diagram
-
-
-
-
?
InsL3 + H2O
InsL3 fragments
show the reaction diagram
-
-
-
-
?
insulin + H2O
?
show the reaction diagram
insulin + H2O
insulin fragments
show the reaction diagram
-
-
-
-
?
insulin + H2O
insulin peptide fragments
show the reaction diagram
insulin-like growth factor I + H2O
insulin-like growth factor I peptide fragments
show the reaction diagram
insulin-like growth factor II + H2O
insulin-like growth factor II peptide fragments
show the reaction diagram
insulin-like growth factor-II + H2O
insulin-like growth factor-II peptide fragments
show the reaction diagram
-
identification of cleavage sites by mass spectrometry and NMR
-
-
?
insulin-like peptide 3 + H2O
processed insulin-like peptide 3 + WSTEA
show the reaction diagram
-
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
-
-
?
reduced amylin + H2O
reduced amylin peptide fragments
show the reaction diagram
-
identification of cleavage sites by mass spectrometry
-
-
?
relaxin + H2O
relaxin fragments
show the reaction diagram
-
-
-
-
?
relaxin-3 + H2O
relaxin-3 fragments
show the reaction diagram
-
-
-
-
?
transforming growth factor-alpha + H2O
transforming growth factor-alpha peptide fragments
show the reaction diagram
-
identification of cleavage sites by mass spectrometry
-
-
?
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
NaCl
-
activates IDE at high concentration
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
((((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
-
-
-
(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
-
1,10-phenanthroline
2,6-dichlorophenol-indophenol
-
uncompetitive
2-mercaptoethanol
-
-
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
-
4,7-phenanthroline
-
-
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
-
bacitracin
beta-gamma-methyleneadenosine 5'-triphosphate
-
65% inhibition
bipyridine
-
-
bradykinin
-
mixed competitive-noncompetitive
Ca2+
-
stimulates cytosolic activity, inhibits particulate activity
Chelating agents
-
-
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
cysteine
-
-
Diamide
-
-
diphosphate
-
46% inhibition
dynorphin B-9
-
inhibitory with insulin as substrate
-
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
hydrogen peroxide
Indole derivatives
-
-
-
Inhibitor from rat liver homogenate
Inhibitors purified from human serum
-
-
-
InsL3
-
competitively inhibits the degradation of insulin, and crosslinking of insulin to IDE
-
Insulin
insulin-like peptide 3
-
IDE degrades insulin quickly, and addition of INSL3 significantly decreases insulin degradation, competitive inhibition
-
Li+
-
inhibits at 1 mM
N-ethylmaleimide
Natural inhibitor of MW 67000 or 80000-120000 MW
-
reduces activity reversibly, nonprogressively, and noncompetitively with respect to insulin
-
nestin
nitric oxide
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
-
-
Phenformin
-
-
phosphorylated vimentin
Proinsulin
protein ANP
-
-
-
protein BNP
-
-
-
protein CNP
-
-
-
protein DNP
-
-
-
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
S-nitrosoglutathione
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
Tolbutamide
-
-
Tryptic fragment of bovine serum albumin
-
-
-
Ub1-72
-
cleaved ubiquitin
-
Ub1-74
-
cleaved ubiquitin
-
ubiquitin
-
-
urodilatin
-
-
-
[(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
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
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
A23187
amyloid beta-peptide 1-40
-
-
-
beta-endorphin
-
-
bradykinin
DTT
-
stimulates
dynorphin A-17
dynorphin B-13
dynorphin B-9
dynorphin B9
-
-
-
glutathione
-
stimulates
Insulin B chain
-
-
Insulin B-chain
-
activation of reaction with substrate 2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine) and amyloid beta-protein
mercaptoethanol
-
stimulates
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
nestin
phosphorylated vimentin
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
Sulfhydryl-dependent enzyme
-
-
-
Triphosphate
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.014 - 0.204
2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine)
0.0066 - 21.3
Abz-GGFLRKHGQ-EDDnp
0.0059 - 0.0254
Abz-GGFLRKHGQEDDnp
0.219
Abz-SEKKDNYIIKGV-nitroY-OH
-
pH 9.2, 37C, recombinant enzyme
0.08
amyloid beta
-
pH 8.0, 37C, 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, 37C
-
0.063
ATP
-
pH 7.4, 37C
4.2
bradykinin
-
pH 7.3, 37C
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 - 0.007
Insulin
0.000055
insulin-like peptide 3
-
pH 7.7, 37C
-
7.3
kallidin
-
pH 7.3, 37C
0.0000244
monoarginine-insulin
-
diarginine-insulin
-
0.0002342 - 0.0008572
Proinsulin
7.5
Somatostatin
-
pH 7.3, 37C
additional information
additional information
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.028
(7-methoxycoumarin-4-yl)acetyl-NPPGFSAFK-2,4-dinitrophenyl
Homo sapiens
-
pH not specified in the publication, 37C
2 - 162600
2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine)
0.003 - 0.258
Abz-GGFLRKHGQ-EDDnp
0.72 - 104
Abz-GGFLRKHGQEDDnp
70
amyloid beta
Homo sapiens
-
pH 8.0, 37C, wild-type enzyme
-
0.0022
amyloid beta-peptide 1-40
Homo sapiens
Q9Y5Z0
pH not specified in the publication, temperature not specified in the publication
-
0.0004
amyloid beta-peptide 1-42
Homo sapiens
Q9Y5Z0
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
Homo sapiens
-
pH 7.3, 37C
-
61 - 62.7
Dabcyl-Tyr-Glu-Val-His-His-Gln-Lys-Leu-Val-Phe-Phe-Ala-Glu-Asp-Val-Gly-Glu(EDANS)-NH2
0.017 - 0.05
Insulin
0.0025
insulin-like peptide 3
Homo sapiens
-
pH 7.7, 37C
-
10
protein ANP
Homo sapiens
-
pH not specified in the publication, 37C
-
0.2
protein BNP
Homo sapiens
-
pH not specified in the publication, 37C
-
20
protein CNP
Homo sapiens
-
pH not specified in the publication, 37C
-
0.1
protein DNP
Homo sapiens
-
pH not specified in the publication, 37C
-
0.38
Somatostatin
Homo sapiens
-
pH 7.3, 37C
2
urodilatin
Homo sapiens
-
pH not specified in the publication, 37C
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.803
amyloid beta-peptide 1-40
Homo sapiens
Q9Y5Z0
pH not specified in the publication, temperature not specified in the publication
34383
0.178
amyloid beta-peptide 1-42
Homo sapiens
Q9Y5Z0
pH not specified in the publication, temperature not specified in the publication
206900
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000045 - 0.00015
ATP
additional information
additional information
-
inhibition kinetics, overview
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
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 37C
-
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 37C
-
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 37C
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 37C
-
0.0014
(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
Homo sapiens
-
in HEPES 50 mM, NaCl 100 mM, pH 7.4, at 37C
-
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 37C
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 37C
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 37C
-
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 37C
-
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 37C
-
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 37C
-
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 37C
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 37C
-
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 37C
-
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 37C
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 37C
-
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 37C
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 37C
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 37C
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 37C
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 37C
-
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 37C
-
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 37C
-
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 37C
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 37C
-
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 37C
-
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 37C
-
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 37C
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 37C
-
0.11 - 0.4
bacitracin
0.9
hydrogen peroxide
Homo sapiens
-
pH 8.0, 37C
0.0000444
InsL3
Rattus norvegicus
-
pH not specified in the publication, temperature not specified in the publication
-
0.04
protein ANP
Homo sapiens
-
pH not specified in the publication, 37C
-
0.12
protein BNP
Homo sapiens
-
pH not specified in the publication, 37C
-
0.07
protein CNP
Homo sapiens
-
pH not specified in the publication, 37C
-
1.3
protein DNP
Homo sapiens
-
pH not specified in the publication, 37C
-
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, 37C
0.001 - 0.1
Ub1-72
0.09
ubiquitin
Homo sapiens
-
pH not specified in the publication, 37C
0.8
urodilatin
Homo sapiens
-
pH not specified in the publication, 37C
-