Summary for 2YPU
| Entry DOI | 10.2210/pdb2ypu/pdb |
| Descriptor | INSULIN-DEGRADING ENZYME, ZINC ION, 2-[[2-[[(2S)-3-(3H-IMIDAZOL-4-YL)-1-METHOXY-1-OXO-PROPAN-2-YL]AMINO]-2-OXO-ETHYL]-(PHENYLMETHYL)AMINO]ETHANOIC ACID, ... (4 entities in total) |
| Functional Keywords | hydrolase, m16a metalloprotease |
| Biological source | HOMO SAPIENS (HUMAN) |
| Cellular location | Cytoplasm: P14735 |
| Total number of polymer chains | 2 |
| Total formula weight | 230000.76 |
| Authors | Guo, Q.,Deprez-Poulain, R.,Deprez, B.,Tang, W.-J. (deposition date: 2012-11-01, release date: 2012-11-28, Last modification date: 2023-12-20) |
| Primary citation | Charton, J.,Gauriot, M.,Guo, Q.,Hennuyer, N.,Marechal, X.,Dumont, J.,Hamdane, M.,Pottiez, V.,Landry, V.,Sperandio, O.,Flipo, M.,Buee, L.,Staels, B.,Leroux, F.,Tang, W.-J.,Deprez, B.,Deprez-Poulain, R. Imidazole-Derived 2-[N-Carbamoylmethyl-Alkylamino]Acetic Acids,Substrate-Dependent Modulators of Insulin-Degrading Enzyme in Amyloid-Beta Hydrolysis Eur J Med Chem, 79C:184-, 2014 Cited by PubMed Abstract: Insulin degrading enzyme (IDE) is a highly conserved zinc metalloprotease that is involved in the clearance of various physiologically peptides like amyloid-beta and insulin. This enzyme has been involved in the physiopathology of diabetes and Alzheimer's disease. We describe here a series of small molecules discovered by screening. Co-crystallization of the compounds with IDE revealed a binding both at the permanent exosite and at the discontinuous, conformational catalytic site. Preliminary structure-activity relationships are described. Selective inhibition of amyloid-beta degradation over insulin hydrolysis was possible. Neuroblastoma cells treated with the optimized compound display a dose-dependent increase in amyloid-beta levels. PubMed: 24735644DOI: 10.1016/J.EJMECH.2014.04.009 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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