4ge9: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older edit
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,330,058 edits
No edit summary
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,330,058 edits
No edit summary
 
(2 intermediate revisions by the same user not shown)
Line 1: Line 1:
==Kynurenine Aminotransferase II Inhibitors==
==Kynurenine Aminotransferase II Inhibitors==
<StructureSection load='4ge9' size='340' side='right' caption='[[4ge9]], [[Resolution|resolution]] 2.43&Aring;' scene=''>
<StructureSection load='4ge9' size='340' side='right'caption='[[4ge9]], [[Resolution|resolution]] 2.43&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4ge9]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GE9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GE9 FirstGlance]. <br>
<table><tr><td colspan='2'>[[4ge9]] is a 4 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=4GE9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GE9 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0L0:(4-{[(6-BENZYL-1-HYDROXY-7-METHOXY-2-OXO-1,2-DIHYDROQUINOLIN-3-YL)AMINO]METHYL}-5-HYDROXY-6-METHYLPYRIDIN-3-YL)METHYL+DIHYDROGEN+PHOSPHATE'>0L0</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.43&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4gdy|4gdy]], [[4ge4|4ge4]], [[4ge7|4ge7]], [[4geb|4geb]], [[3ue8|3ue8]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0L0:(4-{[(6-BENZYL-1-HYDROXY-7-METHOXY-2-OXO-1,2-DIHYDROQUINOLIN-3-YL)AMINO]METHYL}-5-HYDROXY-6-METHYLPYRIDIN-3-YL)METHYL+DIHYDROGEN+PHOSPHATE'>0L0</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=4ge9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ge9 OCA], [https://pdbe.org/4ge9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ge9 RCSB], [https://www.ebi.ac.uk/pdbsum/4ge9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ge9 ProSAT]</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=4ge9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ge9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ge9 RCSB], [http://www.ebi.ac.uk/pdbsum/4ge9 PDBsum]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://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> 
[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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Pandit, J]]
[[Category: Large Structures]]
[[Category: Aminotransferase]]
[[Category: Pandit J]]
[[Category: Irreversible inhibitor]]
[[Category: Transferase-transferase inhibitor complex]]
Retrieved from "https://proteopedia.org/4ge9"