Activating Compound | Comment | Organism | Structure |
---|---|---|---|
ADP | activates, the activating effect of ATP is greater than hat of ADP, which in turn is much greater than that of AMP | Homo sapiens | |
AMP | activates, the activating effect of ATP is greater than hat of ADP, which in turn is much greater than that of AMP | Homo sapiens | |
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 | Homo sapiens | |
CTP | - |
Homo sapiens | |
GTP | - |
Homo sapiens | |
additional information | purine nucleotide triphosphates are better activators than pyrimidine nucleotide triphosphates | Homo sapiens | |
TTP | - |
Homo sapiens |
Cloned (Comment) | Organism |
---|---|
expression of wild-type and mutant enzymes in HEK-293swe.3 cells, that stably expresses Myc-epitope tagged human APP-695 harboring the FAD-linked, socalled Swedish mutation | Homo sapiens |
Crystallization (Comment) | Organism |
---|---|
purified recombinant mutant E11Q in complex with peptide substrate, and substrate-free mutant Y831F, hanging drop vapour diffusion method, 0.001 ml of 15-20 mg/ml protein and 0.001 ml of crystallization solution, containing 10-13% PEGMME 5000, 100 mM HEPES, pH 7.0, 4-14% Tacsimate, and 10% dioxane, are mixed and equilibrated with 0.5 ml of well solution at 18 °C, 3-5 days, cryoprotection by 15-30% glycerol, X-ray diffraction structure determination and analysis at 2.8-3.0 A resolution, modeling | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
D426C/K899C | site-directed mutagenesis, hyperactive IDE mutation, the mutant shows increased activity, but reduced activationby ATP compared to the wild-type enzyme | Homo sapiens |
E111Q | site-directed mutagenesis, inactive mutant | Homo sapiens |
Y831F | site-directed mutagenesis, the mutant shows catalytic activity similar to the wild-type enzyme | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
1,10-phenanthroline | - |
Homo sapiens | |
bacitracin | the inhibitory effect in enhanced by ATP | Homo sapiens |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.025 | - |
amyloid beta-peptide1-40 | recombinant wild-type enzyme, pH 7.4, 37°C | Homo sapiens | |
0.027 | - |
amyloid beta-peptide1-40 | recombinant mutant D426C/K899C, pH 7.4, 37°C | Homo sapiens |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
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 | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
amyloid beta-peptide + H2O | Homo sapiens | degradation, IDE has no effect on the secreted ectodomain of the amyloid precursor protein derivative generated by alpha-secretase | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P14735 | - |
- |
Purification (Comment) | Organism |
---|---|
wild-type and mutant enzymes | Homo sapiens |
Reaction | Comment | Organism | Reaction ID |
---|---|---|---|
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 | Homo sapiens |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
(7-methoxycoumarin-4-yl)acetyl-RPPGFSAFK-2,4-dinitrophenyl + H2O | - |
Homo sapiens | ? | - |
? | |
amyloid beta-peptide + H2O | degradation, IDE has no effect on the secreted ectodomain of the amyloid precursor protein derivative generated by alpha-secretase | Homo sapiens | ? | - |
? | |
amyloid beta-peptide1-40 + H2O | degradation | Homo sapiens | ? | - |
? | |
o-aminobenzoic acid-GGFLRKHGQ-ethylenediamine-2,4-dinitrophenyl + H2O | - |
Homo sapiens | ? | - |
? |
Synonyms | Comment | Organism |
---|---|---|
IDE | - |
Homo sapiens |
Insulin-degrading enzyme | - |
Homo sapiens |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
22 | - |
assay at, substrate o-aminobenzoic acid-GGFLRKHGQ-ethylenediamine-2,4-dinitrophenyl | Homo sapiens |
37 | - |
assay at, substrates amyloid beta-peptide and (7-methoxycoumarin-4-yl)acetyl-RPPGFSAFK-2,4-dinitrophenyl | Homo sapiens |
Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
8 | - |
amyloid beta-peptide1-40 | recombinant wild-type enzyme, pH 7.4, 37°C | Homo sapiens | |
8 | - |
amyloid beta-peptide1-40 | recombinant wild-type enzyme, pH 7.4, 37°C | Triticum aestivum | |
20 | - |
amyloid beta-peptide1-40 | recombinant mutant D426C/K899C, pH 7.4, 37°C | Homo sapiens | |
20 | - |
amyloid beta-peptide1-40 | recombinant mutant D426C/K899C, pH 7.4, 37°C | Triticum aestivum |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.3 | - |
assay at, substrate (7-methoxycoumarin-4-yl)acetyl-RPPGFSAFK-2,4-dinitrophenyl | Homo sapiens |
7.4 | - |
assay at, substrates amyloid beta-peptide and o-aminobenzoic acid-GGFLRKHGQ-ethylenediamine-2,4-dinitrophenyl | Homo sapiens |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.11 | - |
recombinant wild-type enzyme, in in presence of ATP | Homo sapiens | bacitracin | |
0.18 | - |
recombinant mutant D426C/K899C, in in presence of ATP | Homo sapiens | bacitracin | |
0.2 | - |
recombinant mutant D426C/K899C, in absence of ATP | Homo sapiens | bacitracin | |
0.4 | - |
recombinant wild-type enzyme, in absence of ATP | Homo sapiens | bacitracin |