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Enzyme Nomenclature
Information on EC 3.4.24.56 - insulysin
for references in articles please use BRENDA:EC3.4.24.56
Word Map on EC 3.4.24.56
- 3.4.24.56
- alzheimer
- diabetes
-
abeta
- neprilysin
-
cognitive
- hippocampus
- dementia
-
beta-amyloid
- cerebral
- mellitus
-
memory
-
insulin-like
-
senile
-
amyloid-beta
- metalloprotease
- bacitracin
-
endothelin-converting
-
amylin
-
late-onset
- hyperinsulinemia
-
beta-protein
- metallopeptidase
-
maze
- beta-secretase
-
abeta-degrading
- metalloendopeptidase
-
125i-insulin
-
abeta1-40
- gamma-secretase
- b-chains
-
amyloidogenic
-
anti-ide
-
glutathione-insulin
- medicine
-
ad-like
-
exosite
-
beta-peptide
- analysis
-
insulin-receptor
-
enzyme-1
-
proinsulin
-
transhydrogenase
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The enzyme appears in viruses and cellular organisms
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EC NUMBER 
COMMENTARY 
3.4.24.56
-
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RECOMMENDED NAME
GeneOntology No.
insulysin
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Degradation of insulin, glucagon and other polypeptides. No action on proteins
-
-
-
-
Degradation of insulin, glucagon and other polypeptides. No action on proteins
Glu111 serves as a base to activate a catalytic water molecule within the active site of the enzyme, mediating peptide hydrolysis, mutation of this residue to glutamine renders IDE inactive, the catalytic water that is coordinated by a zinc ion also interacts with a glutamate residue, which serves as the general acid/base catalyst, catalytic mechanism
-
Degradation of insulin, glucagon and other polypeptides. No action on proteins
reaction mechanism, active-site model, detailed overview
-
Degradation of insulin, glucagon and other polypeptides. No action on proteins
molecular basis of catalytic chamber-assisted unfolding and cleavage of human insulin by human insulin-degrading enzyme, IDE utilizes the interaction of its exosite with the N-terminus of the insulin A chain, overview. The unique size, shape, charge distribution, and exosite of the IDE catalytic chamber contribute to its high affinity for insulin
-
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
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
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CAS REGISTRY NUMBER
COMMENTARY
9013-83-6
-
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
31303, 31304, 31312, 31313, 31314, 31316, 31326, 31330, 31331, 667436, 667484, 668184, 669956, 670383, 670403, 683094, 683342, 683567, 683568, 683571, 683700, 683751, 683836, 683920, 683921, 683924, 696236, 696530, 697748, 699563, 699678, 700288, 707363, 707402, 708863, 708871, 709016, 709071, 709536, 709705, 710361, 710391, 710486, 710682, 719919, 719995, 720067, 720249, 720293
-
-
healthy individuals and patients with Alzheimer’s disease with cerebral amyloid angiopathy
-
-
isoform IDE-15a using the canonical exon 15a; identification of six distinct enzyme transcripts, in isoform IDE-15b exon 15b replaces the canonical exon 15a
UniProt
-
31312, 31313, 31315, 31317, 31318, 31319, 31320, 31321, 31322, 31323, 31324, 31325, 31326, 31327, 31328, 31330, 31331, 31333, 31335, 31336, 31337, 31339, 31340, 31341, 668492, 669330, 683150, 683920, 696135, 698760, 699416, 700287, 707150, 708463, 710682, 710693, 720045, 720814, 720820, 720829
-
-
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
additional information
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
-
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
-
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
-
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
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 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 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 primary role in insulin degradation and cellular insulin processing
physiological function
-
IDE is an important protease responsible for the degradation of amyloid-beta in neural cells
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
-
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 important in maintaining insulin levels and in insulin catabolism
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
the enzyme provokes growth reduction mediated by the phosphatidylinositol-3-phosphate kinase pathway in a cell-autonomous manner
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 Alzheimer’s disease
additional information
-
interplay between retinoblastoma tumor suppressor protein and IDE within the proteasome that may have important growth-regulatory consequences
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
-
IDE activity protects against Alzheimer's disease, IDE suppression of IDE induces the pathology
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(7-methoxycoumarin-4-yl)acetyl-NPPGFSAFK-2,4-dinitrophenyl + H2O
?
-
bradykinin mimetic substrate V
-
-
?
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-ethylenediamine-2,4-dinitrophenyl + H2O
2-aminobenzoyl-GGFLR + KHGQ-ethylenediamine-2,4-dinitrophenyl
-
-
-
-
?
7-methoxycoumarin-4-yl-acetyl-RPPGFSAFK-2,4-dinitrophenyl + H2O
?
-
fluorogenic bradykinin-mimetic IDE substrate V
-
-
?
Abz-SEKKDNYIIKGV-nitroY-OH + H2O
?
-
a substrate based on the polypeptide sequence of the yeast P2 a-factor mating propheromone
-
-
?
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 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
-
-
?
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
-
-
?
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
-
insulin-like growth factor-II + H2O
insulin-like growth factor-II peptide fragments
-
identification of cleavage sites by mass spectrometry and NMR
-
-
?
o-aminobenzoic acid-GGFLRKHGQ-ethylenediamine-2,4-dinitrophenyl + 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
-
-
-
reduced amylin + H2O
reduced amylin peptide fragments
-
identification of cleavage sites by mass spectrometry
-
-
?
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
-
-
?
(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
?
-
-
-
-
?
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
-
synthetic fluorogenic substrate
-
-
?
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 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
?
-
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
?
-
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, 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
?
-
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 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 beta42 + H2O
amyloid beta42 peptide fragments
-
Abeta42, an Alzheimer amyloid beta peptide
-
-
?
amyloid beta42 + H2O
amyloid beta42 peptide fragments
-
an Alzheimer amyloid beta peptide
-
-
?
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
-
-
?
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
-
-
?
Glucagon + H2O
Hydrolyzed glucagon
-
-
appearance of: tyrosine, leucine, lysine, alanine and phenylalanine
-
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
?
-
the enzyme may play a general role in hormone metabolism and cellular regulation
-
-
-
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
?
-
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
?
-
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
?
-
implicated in the process of membrane fusion and cell development
-
-
-
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, reduced insulin degradation leads to type 2 diabetes, regulation, overview
-
-
?
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
?
-
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
?
-
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
-
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
-
-
-
-
-
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
-
-
31312, 31313, 31315, 31317, 31318, 31320, 31321, 31322, 31323, 31324, 31325, 31326, 31327, 31328, 31330, 31331, 31333, 31337, 31339, 31340
-
-
-
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
insulin peptide fragments
-
-
-
-
?
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
-
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
-
IDE uses the size and charge distribution of the catalytic chamber and structural flexibility of the substrates to selectively recognize and degrade insulin
-
-
?
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
-
-
?
peptide V + H2O
?
-
a bradykinin-mimetic fluorogenic peptide substrate V
-
-
?
peptide V + H2O
?
-
a bradykinin-mimetic fluorogenic peptide substrate V
-
-
?
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
?
-
-
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 Alzheimer’s 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 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
?
-
-
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
?
-
-
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
?
-
-
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
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
amyloid beta42 + H2O
amyloid beta42 peptide fragments
-
Abeta42, an Alzheimer amyloid beta peptide
-
-
?
ATP + H2O
ADP + phosphate
-
insulin-binding and degradation are dependent on ATP concentration, however, insulin does not modify the ATPase activity of IDE
-
-
?
epidermal growth factor + H2O
epidermal growth factor peptide fragments
-
identification of cleavage sites by mass spectrometry and NMR
-
-
?
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
-
-
?
reduced amylin + H2O
reduced amylin peptide fragments
-
identification of cleavage sites by mass spectrometry
-
-
?
transforming growth factor-alpha + H2O
transforming growth factor-alpha peptide fragments
-
identification of cleavage sites by mass spectrometry
-
-
?
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-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
?
P14735
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, 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, 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
-
-
?
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
?
-
the enzyme may play a general role in hormone metabolism and cellular regulation
-
-
-
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
?
-
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
?
-
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
?
-
implicated in the process of membrane fusion and cell development
-
-
-
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, reduced insulin degradation leads to type 2 diabetes, regulation, overview
-
-
?
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
?
-
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
-
rapid degradation into inactive 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 Alzheimer’s 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 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
?
-
-
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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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Mg2+
Mn2+
thiol
Zinc
Zn2+
additional information
Mg2+
-
activates at concentration up to 0.05 mM, less active than Mn2+, inhibitory at above 0.05 mM
Mn2+
-
zinc and manganese are associated with the enzyme, with approximately 10times more zinc than manganese being present, one or both of these two metals are endogenously associated with this enzyme
Mn2+
-
zinc and manganese are associated with the enzyme, with approximately 10times more zinc than manganese being present, one or both of these two metals are endogenously associated with this enzyme
Mn2+
-
activates, best at 1 mM, preferred divalent cation for both insulin degradation and ATP hydrolysis
thiol
-
the enzyme is a neutral thiol metalloprotease requiring both free thiol and divalent cations for activity
thiol
-
the enzyme is a neutral thiol metalloprotease requiring both free thiol and divalent cations for activity
thiol
-
the enzyme is a neutral thiol metalloprotease requiring both free thiol and divalent cations for activity
Zinc
-
zinc and manganese are associated with the enzyme, with approximately 10times more zinc than manganese being present, one or both of these two metals are endogenously associated with this enzyme
Zinc
-
zinc and manganese are associated with the enzyme, with approximately 10times more zinc than manganese being present, one or both of these two metals are endogenously associated with this enzyme
Zn2+
-
a zinc metalloprotease, the catalytic water that is coordinated by a zinc ion also interacts with a glutamate residue, which serves as the general acid/base catalyst
Zn2+
-
the enzyme is a neutral thiol metalloprotease requiring both free thiol and divalent cations for activity
Zn2+
-
dependent on, zinc metallopeptidase, simulated structures of the Zn2+ metal center, overview
Zn2+
-
a zinc-binding protease. The metal center in human IDE is chelated by His108, His112, and Glu189. The more external residues Tyr831, Glu111, Thr220, Gly221, Glu182, and Arg824 are also determined. Among these last residues, mainly Glu182, although not directly involved as metal ligand, plays a fundamental role in influencing metal recognition and binding by zinc proteins
Zn2+
-
the enzyme is a neutral thiol metalloprotease requiring both free thiol and divalent cations for activity
Zn2+
-
one Zn2+ bound at the active site, with the zinc-binding motif HXXEH
Zn2+
-
the enzyme is a neutral thiol metalloprotease requiring both free thiol and divalent cations for activity
additional information
-
metalloenzyme, removal of the protein-bound metal(s) results in nearly total and irreversible loss of activity
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
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
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
adrenocorticotropic hormone
-
competitive inhibition of amylin degradation
-
amylin
-
excess amylin inhibits amylin degradation, competitive inhibition
-
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
glutathione
-
oxidized glutathione inhibits IDE through glutathionylation, which is reversible by dithiothreitol but not by ascorbic acid
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
-
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
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
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
[(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
-
Zn2+, Co2+, Mn2+ and to a smaller extent Cd2+ and Fe2+ are capable of preventing the inhibition
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
EDTA
-
the activation of IDE disappears upon inactivation by EDTA, which chelates the catalytic Zn2+ ion
EDTA
-
0.1 mM, wild-type, 91% residual activity, mutants H112D, H112Q, less than 2.5% residual activity
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
-
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
-
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
-
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
-
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: 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.
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
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
Insulin B-chain
-
activation of reaction with substrate 2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine) and amyloid beta-protein
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
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
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
-
inhibition of binding of 2’,3’-O-(2,4,6-trinitrophenyl)adenosine triphosphate with Ki-value 2.2 mM
ADP
-
in Tris buffer, activation for substrate 2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine). Activation in decreasing order: ATP, triphosphate, ADP, AMP
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
bradykinin
-
activation of reaction with substrate 2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine) and amyloid beta-protein
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
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
-
Triphosphate
-
inhibition of binding of 2’,3’-O-(2,4,6-trinitrophenyl)adenosine triphosphate with Ki-value 0.9 mM
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
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.
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
-
1.2 - 2.3
Dabcyl-Tyr-Glu-Val-His-His-Gln-Lys-Leu-Val-Phe-Phe-Ala-Glu-Asp-Val-Gly-Glu(EDANS)-NH2
0.014
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
0.0066
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
0.0148
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
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
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
0.0001
Insulin
-
pH not specified in the publication, temperature not specified in the publication
-
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
-
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
-
with substrate 2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine), enzyme exhibits allosteric kinetics
-
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
-
additional information
additional information
-
amyloid beta degradation kinetics in presence or absence of activators
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.028
(7-methoxycoumarin-4-yl)acetyl-NPPGFSAFK-2,4-dinitrophenyl
-
pH not specified in the publication, 37°C
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
-
61 - 62.7
Dabcyl-Tyr-Glu-Val-His-His-Gln-Lys-Leu-Val-Phe-Phe-Ala-Glu-Asp-Val-Gly-Glu(EDANS)-NH2
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
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; 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; 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
0.06
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
0.258
Abz-GGFLRKHGQ-EDDnp
-
mutant K898A/K899A/S901A, pH and temperature not specified in the publication
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
20
amyloid beta-peptide1-40
-
recombinant mutant D426C/K899C, 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
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.803
amyloid beta-peptide 1-40
pH not specified in the publication, temperature not specified in the publication
-
0.178
amyloid beta-peptide 1-42
pH not specified in the publication, temperature not specified in the publication
-
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
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 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