4ge7
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Kynurenine Aminotransferase II Inhibitors== | |
| + | <StructureSection load='4ge7' size='340' side='right'caption='[[4ge7]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4ge7]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GE7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GE7 FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0K5:(5-HYDROXY-4-{[(1-HYDROXY-2-OXO-6-PHENOXY-1,2-DIHYDROQUINOLIN-3-YL)AMINO]METHYL}-6-METHYLPYRIDIN-3-YL)METHYL+DIHYDROGEN+PHOSPHATE'>0K5</scene>, <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ge7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ge7 OCA], [https://pdbe.org/4ge7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ge7 RCSB], [https://www.ebi.ac.uk/pdbsum/4ge7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ge7 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/AADAT_HUMAN 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).<ref>PMID:18620547</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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<ref>PMID:24900560</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 4ge7" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Pandit J]] | ||
Current revision
Kynurenine Aminotransferase II Inhibitors
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