Crystallization (Comment) | Organism |
---|---|
X-ray diffraction structure determination and analysis of enzyme-substrate complexes IDE-IGF-II and IDE-TGF-alpha at 2.3 A resolution and IDE-amylin at 2.9 A resolution | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
amylin + H2O | Homo sapiens | 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 | amylin peptide fragments | - |
? | |
amyloid beta + H2O | Homo sapiens | - |
amyloid beta peptide fragments | - |
? | |
epidermal growth factor + H2O | Homo sapiens | identification of cleavage sites by mass spectrometry and NMR | epidermal growth factor peptide fragments | - |
? | |
insulin + H2O | Homo sapiens | - |
insulin peptide fragments | - |
? | |
insulin-like growth factor-II + H2O | Homo sapiens | identification of cleavage sites by mass spectrometry and NMR | insulin-like growth factor-II peptide fragments | - |
? | |
additional information | Homo sapiens | 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 | ? | - |
? | |
reduced amylin + H2O | Homo sapiens | identification of cleavage sites by mass spectrometry | reduced amylin peptide fragments | - |
? | |
transforming growth factor-alpha + H2O | Homo sapiens | identification of cleavage sites by mass spectrometry | transforming growth factor-alpha peptide fragments | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Reaction | Comment | Organism | Reaction ID |
---|---|---|---|
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 | Homo sapiens |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
amylin + H2O | 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 | Homo sapiens | amylin peptide fragments | - |
? | |
amyloid beta + H2O | - |
Homo sapiens | amyloid beta peptide fragments | - |
? | |
epidermal growth factor + H2O | identification of cleavage sites by mass spectrometry and NMR | Homo sapiens | epidermal growth factor peptide fragments | - |
? | |
insulin + H2O | - |
Homo sapiens | insulin peptide fragments | - |
? | |
insulin-like growth factor-II + H2O | identification of cleavage sites by mass spectrometry and NMR | Homo sapiens | insulin-like growth factor-II peptide fragments | - |
? | |
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 | Homo sapiens | ? | - |
? | |
reduced amylin + H2O | identification of cleavage sites by mass spectrometry | Homo sapiens | reduced amylin peptide fragments | - |
? | |
transforming growth factor-alpha + H2O | identification of cleavage sites by mass spectrometry | Homo sapiens | transforming growth factor-alpha peptide fragments | - |
? |
Synonyms | Comment | Organism |
---|---|---|
IDE | - |
Homo sapiens |
Insulin-degrading enzyme | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
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 | Homo sapiens |