4dtt | pdb_00004dtt

Crystal structure of human insulin degrading enzyme (ide) in complex with compund 41367

spinqualitylabelsall models 4dtt, resolution 3.22Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4dtt is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: I41, ZN Related: 4dtv Gene: IDE (HUMAN) Activity: Insulysin, with EC number 3.4.24.56 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed 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. Imidazole-derived 2-[N-carbamoylmethyl-alkylamino]acetic acids, substrate-dependent modulators of insulin-degrading enzyme in amyloid-beta hydrolysis.,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 WJ, Deprez B, Deprez-Poulain R Eur J Med Chem. 2014 Apr 4;79C:184-193. doi: 10.1016/j.ejmech.2014.04.009. PMID:24735644 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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