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Literature summary for 3.4.24.56 extracted from
- Protective role of Cys-178 against the inactivation and oligomerization of human insulin-degrading enzyme by oxidation and nitrosylation (2009), J. Biol. Chem., 284, 34005-34018.
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| expressed in BV-2 cells | Homo sapiens |
| expression of His-tagged wild-type and mutant IDEs in Escherichia coli strain Rosetta (DE3) | Homo sapiens |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| additional information | construction of Cys residue mutants of IDE, properties of oxidized and/or nitrosylated mutant enzymes compared to wild-type enzyme, overview | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| 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 | Homo sapiens |  |
| NEM | modifies Cys819 and inhibits IDE | Homo sapiens | |
| 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 | Homo sapiens | |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 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 | Homo sapiens | |
| 0.08 | - |
amyloid beta | pH 8.0, 37°C, wild-type enzyme | Homo sapiens |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| extracellular | IDE is secreted by BV-2 microglial cells | Homo sapiens | - |
- |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Zn2+ | dependent on, metallopeptidase | Homo sapiens | |
Molecular Weight [Da]
| Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
|---|---|---|---|
| 110000 | - |
monomeric enzyme | Homo sapiens |
| 150000 | - |
monomer/dimer mixture of solubilized enzyme, gel filtration | Homo sapiens |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| amyloid beta + H2O | Homo sapiens | - |
amyloid beta peptide fragments | - |
? | |
| insulin + H2O | Homo sapiens | - |
insulin peptide fragments | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| recombinant His-tagged wild-type and mutant IDEs from Escherichia coli strain Rosetta (DE3) by nickel affinity chromatography | Homo sapiens |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| microglia | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| amyloid beta + H2O | - |
Homo sapiens | amyloid beta peptide fragments | - |
? | |
| insulin + H2O | - |
Homo sapiens | insulin peptide fragments | - |
? | |
| peptide V + H2O | a bradykinin-mimetic fluorogenic peptide substrate V | Homo sapiens | ? | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| monomer or dimer | in solution the enzyme exists as a monomer/dimer mixture | Homo sapiens |
| More | oligomeric forms of IDE treated with H2O2 and GSN, 280-290 kDa, overview | Homo sapiens |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| IDE | - |
Homo sapiens |
| Insulin-degrading enzyme | - |
Homo sapiens |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 37 | - |
assay at | Homo sapiens |
Temperature Stability [°C]
| Temperature Stability Minimum [°C] | Temperature Stability Maximum [°C] | Comment | Organism |
|---|---|---|---|
| additional information | - |
the oxidative burst of BV-2 microglial cells leads to oxidation or nitrosylation of secreted IDE, leading to decreased IDE thermostability | Homo sapiens |
Turnover Number [1/s]
| Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 70 | - |
amyloid beta | pH 8.0, 37°C, wild-type enzyme | Homo sapiens |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 8 | - |
assay at | Homo sapiens |
Ki Value [mM]
| Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
|---|---|---|---|---|---|
| additional information | - |
additional information | inhibition kinetics, overview | Homo sapiens |
IC50 Value
| IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|
| 0.9 | - |
pH 8.0, 37°C | Homo sapiens | hydrogen peroxide | |
| 1.2 | - |
pH 8.0, 37°C | Homo sapiens | S-nitrosoglutathione | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| 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 | Homo sapiens |
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