4GSC
Structure analysis of insulin degrading enzyme with compound bdm41559 ((s)-2-[2-(carboxymethyl-phenethyl-amino)-acetylamino]-3-(1h-imidazol-4-yl)-propionic acid methyl ester)
Summary for 4GSC
| Entry DOI | 10.2210/pdb4gsc/pdb |
| Related | 4GS8 4GSE 4GSF |
| Descriptor | Insulin-degrading enzyme, ZINC ION, methyl N-(carboxymethyl)-N-(2-phenylethyl)glycyl-L-histidinate, ... (4 entities in total) |
| Functional Keywords | insulin degrading enzyme, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm: P14735 |
| Total number of polymer chains | 2 |
| Total formula weight | 230028.81 |
| Authors | Guo, Q.,Deprez-Poulain, R.,Deprez, B.,Tang, W.J. (deposition date: 2012-08-27, release date: 2013-08-28, Last modification date: 2023-09-13) |
| 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., 79:184-193, 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 (2.81 Å) |
Structure validation
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