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Literature summary for 3.4.24.56 extracted from
- Mixed dimers of insulin-degrading enzyme reveal a cis activation mechanism (2011), J. Biol. Chem., 286, 13853-13858.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| bradykinin | - |
Homo sapiens |  |
| dynorphin B9 | - |
Homo sapiens | |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| IDE is expressed in Sf9 insect cells by using baculovirus system | Homo sapiens |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| E111F | a mixed dimer in which one subunit contains the wild-type sequence and the other contains a E111F mutation that permits substrate binding, but not catalysis (E111F), exhibits a decrease in turnover number. A mixed dimer consisting of IDE:mutant E111F/Y609F IDE shows a high reduction in kcat, Km (Abz-GGFLRKHGQ-EDDnp) is 66% reduced compared to wild-type. Mixed dimer IDE:mutant E111F in which the inactive subunit can bind substrate exhibites a decreased activity than wild-type IDE towards substrate amyloid beta peptide | Homo sapiens |
| H112Q | a mixed dimer composed of one wild-type subunit and the other subunit containing a H112Q mutation that neither permits substrate binding nor catalysis exhibits the same turnover number per active subunit as wild-type IDE. Mixed oligomer IDE:IDE mutant H112Q shows similar kcat and Km (Abz-GGFLRKHGQ-EDDnp) compared to wild-type. Mixed dimer IDE:mutant H112Q IDE in which the inactive subunit does not bind substrate exhibits a slightly higher activity than wild-type IDE towards substrate amyloid beta peptide | Homo sapiens |
| Y609F | mutation Y609F in the distal part of the substrate binding site of the active subunit blocks allosteric activation regardless of the activity of the other subunit. A mixed dimer consisting of mutant Y609F IDE: mutant E111F IDE shows a high reduction in kcat and a reduction in Km compared to wild-type. A mixed dimer consisting of mutant Y609F IDE: mutant E111F/Y609F IDE shows a high reduction in kcat, Km (Abz-GGFLRKHGQ-EDDnp) is 50% reduced compared to wild-type. Substrate amyloid beta peptide: When the distal site is mutated on both subunits (Y609F IDE:IDE Y609F) there is an even greater decrease in the reaction rate | Homo sapiens |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.0091 | - |
Abz-GGFLRKHGQ-EDDnp | pH 7.4, 37°C, IDE:IDE mutant E111F/Y609F | Homo sapiens | |
| 0.0109 | - |
Abz-GGFLRKHGQ-EDDnp | pH 7.4, 37°C, mutant Y609F IDE:IDE mutant E111F | Homo sapiens | |
| 0.0113 | - |
Abz-GGFLRKHGQ-EDDnp | pH 7.4, 37°C, mutant Y609F IDE:IDE mutant H112Q | Homo sapiens | |
| 0.0135 | - |
Abz-GGFLRKHGQ-EDDnp | pH 7.4, 37°C, IDE:IDE mutant H112Q/Y609F | Homo sapiens | |
| 0.0148 | - |
Abz-GGFLRKHGQ-EDDnp | pH 7.4, 37°C, mutant Y609F IDE:IDE mutant E111F/Y609F | Homo sapiens | |
| 0.0192 | - |
Abz-GGFLRKHGQ-EDDnp | pH 7.4, 37°C, mutant Y609F IDE:IDE mutant H112Q/Y609F | Homo sapiens | |
| 0.0217 | - |
Abz-GGFLRKHGQ-EDDnp | pH 7.4, 37°C, IDE:IDE mutant E111F | Homo sapiens | |
| 0.0232 | - |
Abz-GGFLRKHGQ-EDDnp | pH 7.4, 37°C, IDE:IDE mutant H112Q | Homo sapiens | |
| 0.0268 | - |
Abz-GGFLRKHGQ-EDDnp | pH 7.4, 37°C, mutant Y609F IDE:IDE mutant Y609F | Homo sapiens | |
| 0.0315 | - |
Abz-GGFLRKHGQ-EDDnp | pH 7.4, 37°C, IDE:IDE, wild-type | Homo sapiens | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| using Ni-affinity chromatography | Homo sapiens |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| Abz-GGFLRKHGQ-EDDnp + H2O | substrate or small peptide activation occurs through a cis effect | Homo sapiens | Abz-GGFLR + KHGQ-EDDnp | - |
? | |
| amyloid beta-peptide + H2O | activation in trans is observed with extended substrates that occupy both the active and distal sites | Homo sapiens | ? | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| dimer | - |
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 |
Turnover Number [1/s]
| Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.003 | - |
Abz-GGFLRKHGQ-EDDnp | pH 7.4, 37°C, mutant Y609F IDE:IDE mutant E111F/Y609F | Homo sapiens | |
| 0.01 | - |
Abz-GGFLRKHGQ-EDDnp | pH 7.4, 37°C, IDE:IDE mutant E111F/Y609F | Homo sapiens | |
| 0.01 | - |
Abz-GGFLRKHGQ-EDDnp | pH 7.4, 37°C, mutant Y609F IDE:IDE mutant E111F | Homo sapiens | |
| 0.03 | - |
Abz-GGFLRKHGQ-EDDnp | pH 7.4, 37°C, IDE:IDE mutant H112Q/Y609F | Homo sapiens | |
| 0.03 | - |
Abz-GGFLRKHGQ-EDDnp | pH 7.4, 37°C, mutant Y609F IDE:IDE mutant Y609F | Homo sapiens | |
| 0.05 | - |
Abz-GGFLRKHGQ-EDDnp | pH 7.4, 37°C, mutant Y609F IDE:IDE mutant H112Q | Homo sapiens | |
| 0.06 | - |
Abz-GGFLRKHGQ-EDDnp | pH 7.4, 37°C, mutant Y609F IDE:IDE mutant H112Q/Y609F | Homo sapiens | |
| 0.12 | - |
Abz-GGFLRKHGQ-EDDnp | pH 7.4, 37°C, IDE:IDE mutant H112Q | Homo sapiens | |
| 0.14 | - |
Abz-GGFLRKHGQ-EDDnp | pH 7.4, 37°C, IDE:IDE, wild-type | Homo sapiens | |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 7.4 | - |
assay at | Homo sapiens |
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