3.4.24.56: insulysin
This is an abbreviated version!
For detailed information about insulysin, go to the full flat file.
Word Map on EC 3.4.24.56
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3.4.24.56
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alzheimer
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neprilysin
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abeta
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hippocampus
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dementia
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mellitus
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cerebral
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morris
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amyloid-beta
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metalloprotease
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maze
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neuroprotective
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amyloidogenic
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tau
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beta-amyloid
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neurodegenerative
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presenilin
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endothelin-converting
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senile
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gamma-secretase
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beta-protein
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125i-insulin
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abeta-degrading
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hyperinsulinemia
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metalloendopeptidase
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bacitracin
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beta-secretase
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late-onset
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amylin
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microglia
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medicine
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adam10
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non-amyloidogenic
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glutathione-insulin
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enzyme-1
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b-chains
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analysis
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ad-like
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anti-ide
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exosite
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beta-peptide
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abeta1-40
- 3.4.24.56
- alzheimer
- neprilysin
- abeta
- hippocampus
- dementia
- mellitus
- cerebral
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morris
- amyloid-beta
- metalloprotease
-
maze
-
neuroprotective
-
amyloidogenic
- tau
- beta-amyloid
- neurodegenerative
-
presenilin
-
endothelin-converting
-
senile
- gamma-secretase
- beta-protein
- 125i-insulin
-
abeta-degrading
- hyperinsulinemia
- metalloendopeptidase
- bacitracin
- beta-secretase
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late-onset
- amylin
- microglia
- medicine
- adam10
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non-amyloidogenic
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glutathione-insulin
- enzyme-1
- b-chains
- analysis
-
ad-like
-
anti-ide
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exosite
- beta-peptide
- abeta1-40
Reaction
Degradation of insulin, glucagon and other polypeptides. No action on proteins =
Synonyms
ADE, amyloid degrading enzyme, cgd6_5510, EC 3.4.22.11, EC 3.4.99.10, EC 3.4.99.45, gamma-endorphin-generating enzyme, IDE, INS20-19, insulin degrading enzyme, Insulin protease, Insulin proteinase, Insulin-degrading enzyme, Insulin-degrading neutral proteinase, Insulin-glucagon protease, Insulin-specific protease, Insulinase, Insulysin, Metalloinsulinase, More, pitrilysin metallopeptidase 1, Pitrm1
ECTree
3.4.24.56 insulysinAdvanced search results
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results (Activating Compound
Activating Compound on EC 3.4.24.56 - insulysin
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ACTIVATING COMPOUND 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
IMAGE
1-diphosphoinositol pentakisphosphate
activates, maximal 79.7fold activation
2',3'-O-(2,4,6-trinitrophenyl)adenosine triphosphate
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about 15fold activation, 50% activation at o.0016 mM, activation is inhibited by Mg2+
2'-O-(2,4,6-trinitrophenyl) adenosine triphosphate
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ATP-derivative TNP-ATP
3'-O-(2,4,6-trinitrophenyl) adenosine triphosphate
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ATP-derivative TNP-ATP
5-(4-chlorophenyl)-2-[(E)-{[(5-chloro-1,2,3-thiadiazol-4-yl)methoxy]imino}methyl]cyclohexane-1,3-dione
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direct stimulation of IDE, acts highly synergistically with ATP, Ia1 activates the degradation of amyloid beta by about 700% in presence other shorter substrates
5-diphosphoinositol pentakisphosphate
activates, maximal 94.7fold activation
alpha-synuclein
a peptide with the C-terminal 44 residues of alpha-synuclein increases insulin-degrading enzyme proteolysis to the same degree as full-length alpha-synuclein. A peptide containing the first 97 residues of alpha-synuclein does not improve insulin-degrading enzyme activity. Because the alpha-synuclein C-terminus is acidic, the interaction appears to involve electrostatic attraction with basic exosite of insulin-degrading enzyme
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Insulin B-chain
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activation of reaction with substrate 2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine) and amyloid beta-protein
myoinositol 1,2,3,4,5,6-hexakisphosphate
i.e. phytic acid, maximal 72fold activation
myoinositol 1,3,4,5,6-pentakisphosphate
activates, maximal 83.3fold activation
myoinositol 1,3,4,5-tetrakisphosphate
activates, maximal 58.6fold activation
myoinositol 1,3,5-trisphosphate
activates, maximal 12.9fold activation
myoinositol 1,4,5-trisphosphate
activates, maximal 30.6fold activation
N-(3-chlorophenyl)-4-[5-(furan-2-yl)-1H-pyrazol-3-yl]piperidine-1-carboxamide
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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
resveratrol
incubation with resveratrol results in a substantial increase in Abeta42 fragmentation compared to the control, signifying that the polyphenol sustains insulin-degrading enzyme-dependent degradation of Abeta42 and its fragments
A23187
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calcium ionophore, increases extracellular IDE activity, but only under conditions that also elicit cytotoxicity
A23187
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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
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in Tris buffer, activation for substrate 2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine). Activation in decreasing order: ATP, triphosphate, ADP, AMP
ADP
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inhibition of binding of 2,3-O-(2,4,6-trinitrophenyl)adenosine triphosphate with Ki-value 2.2 mM
AMP
activates, the activating effect of ATP is greater than hat of ADP, which in turn is much greater than that of AMP
AMP
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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
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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
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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
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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
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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
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activation of reaction with substrate 2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine) and amyloid beta-protein
dynorphin A-17
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activation of reaction with substrate 2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine) and amyloid beta-protein
dynorphin B-13
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activation of reaction with substrate 2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine) and amyloid beta-protein
dynorphin B-9
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activation of reaction with substrate 2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine) and amyloid beta-protein
nestin
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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
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nestin
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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
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phosphorylated vimentin
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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
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phosphorylated vimentin
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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
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Somatostatin
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somatostatin binding to IDE brings about a concentration-dependent structural change of the secondary and tertiary structure of the enzyme, revealing two possible binding sites. The higher affinity binding site disappears upon inactivation of IDE by ethylenediaminetetraacetic acid, which chelates the catalytic Zn2+ ion
Somatostatin
enhances the proteolytic processing of a synthetic beta-amyloid-peptide. In addition to being a substrate, somatostatin is also able to bind to two additional exosites, which play different roles according to the size of the substrate and its binding mode to the catalytic cleft of the enzyme. One exosite, which displays high affinity for somatostatin, regulates only the interaction of insulin-degrading-enzyme with larger substrates (such as insulin and beta-amyloid1-40) in a differing fashion according to their various modes of binding to the enzyme. A second exosite, which is involved in the regulation of enzymatic processing by the enzyme of all substrates investigated (including a 10-25 amino acid long amyloid-like peptide, bradykinin and somatostatin itself), probably acts through the alteration of an open-closed equilibrium
Triphosphate
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in Tris buffer, up to 20fold activation for substrate 2-aminobenzoyl-GGFLRKHGQ-(N-(2,4-dinitrophenyl)ethylenediamine), noncompetitive activator. Activation in decreasing order: ATP, triphosphate, ADP, AMP. Up to 10fold activation with substrates bradykinin, dynorphin B-9. No activation with substrates insulin or amyloid beta-protein
Triphosphate
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inhibition of binding of 2,3-O-(2,4,6-trinitrophenyl)adenosine triphosphate with Ki-value 0.9 mM
additional information
purine nucleotide triphosphates are better activators than pyrimidine nucleotide triphosphates
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additional information
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purine nucleotide triphosphates are better activators than pyrimidine nucleotide triphosphates
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additional information
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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
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additional information
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synthesis and analysis of synthetic small-molecule activators, structure-activity relationships, overview
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additional information
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fibrillar amyloid beta-peptide induces the enzyme in astrocytes through activation of a MAPK cascade via ERK1/2
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