4ge7

Kynurenine Aminotransferase II Inhibitors

spinqualitylabelsall models 4ge7, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ge7 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.1Å Ligands: 0K5, CSO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function AADAT_HUMAN Transaminase with broad substrate specificity. Has transaminase activity towards aminoadipate, kynurenine, methionine and glutamate. Shows activity also towards tryptophan, aspartate and hydroxykynurenine. Accepts a variety of oxo-acids as amino-group acceptors, with a preference for 2-oxoglutarate, 2-oxocaproic acid, phenylpyruvate and alpha-oxo-gamma-methiol butyric acid. Can also use glyoxylate as amino-group acceptor (in vitro). Publication Abstract from PubMed A series of aryl hydroxamates recently have been disclosed as irreversible inhibitors of kynurenine amino transferase II (KAT II), an enzyme that may play a role in schizophrenia and other psychiatric and neurological disorders. The utilization of structure-activity relationships (SAR) in conjunction with X-ray crystallography led to the discovery of hydroxamate 4, a disubstituted analogue that has a significant potency enhancement due to a novel interaction with KAT II. The use of k inact/K i to assess potency was critical for understanding the SAR in this series and for identifying compounds with improved pharmacodynamic profiles. Structure-Based Design of Irreversible Human KAT II Inhibitors: Discovery of New Potency-Enhancing Interactions.,Tuttle JB, Anderson M, Bechle BM, Campbell BM, Chang C, Dounay AB, Evrard E, Fonseca KR, Gan X, Ghosh S, Horner W, James LC, Kim JY, McAllister LA, Pandit J, Parikh VD, Rago BJ, Salafia MA, Strick CA, Zawadzke LE, Verhoest PR ACS Med Chem Lett. 2012 Oct 24;4(1):37-40. doi: 10.1021/ml300237v. eCollection, 2013 Jan 10. PMID:24900560 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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