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4ge4

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Revision as of 22:09, 4 August 2016

Kynurenine Aminotransferase II Inhibitors

Structural highlights

4ge4 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:
Related:	4gdy, 4ge9, 4ge7, 4geb, 3ue8
Gene:	AADAT, KAT2 (HUMAN)
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).^[1]

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Han Q, Cai T, Tagle DA, Robinson H, Li J. Substrate specificity and structure of human aminoadipate aminotransferase/kynurenine aminotransferase II. Biosci Rep. 2008 Aug;28(4):205-15. PMID:18620547 doi:10.1042/BSR20080085
↑ 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. Structure-Based Design of Irreversible Human KAT II Inhibitors: Discovery of New Potency-Enhancing Interactions. ACS Med Chem Lett. 2012 Oct 24;4(1):37-40. doi: 10.1021/ml300237v. eCollection, 2013 Jan 10. PMID:24900560 doi:http://dx.doi.org/10.1021/ml300237v

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4ge4"

Categories: Human | Pandit, J | Aminotransferase | Irreversible inhibitor | Transferase-transferase inhibitor complex

@@ Line 1: / Line 1: @@
 ==Kynurenine Aminotransferase II Inhibitors==
 <StructureSection load='4ge4' size='340' side='right' caption='[[4ge4]], [[Resolution|resolution]] 2.41&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4gdy|4gdy]], [[4ge9|4ge9]], [[4ge7|4ge7]], [[4geb|4geb]], [[3ue8|3ue8]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AADAT, KAT2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ge4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ge4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ge4 RCSB], [http://www.ebi.ac.uk/pdbsum/4ge4 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ge4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ge4 OCA], [http://pdbe.org/4ge4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ge4 RCSB], [http://www.ebi.ac.uk/pdbsum/4ge4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ge4 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4ge4" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4ge4

From Proteopedia

Revision as of 22:09, 4 August 2016

Kynurenine Aminotransferase II Inhibitors

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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