4geb

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==Kynurenine Aminotransferase II Inhibitors==
==Kynurenine Aminotransferase II Inhibitors==
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<StructureSection load='4geb' size='340' side='right' caption='[[4geb]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
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<StructureSection load='4geb' size='340' side='right'caption='[[4geb]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4geb]] is a 2 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=4GEB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GEB FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4geb]] 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=4GEB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GEB FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0LD:(5-HYDROXY-4-{[(7-HYDROXY-6-OXO-2-PHENYL-6,7-DIHYDRO-2H-PYRAZOLO[3,4-B]PYRIDIN-5-YL)AMINO]METHYL}-6-METHYLPYRIDIN-3-YL)METHYL+DIHYDROGEN+PHOSPHATE'>0LD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.15&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4gdy|4gdy]], [[4ge4|4ge4]], [[4ge7|4ge7]], [[4ge9|4ge9]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0LD:(5-HYDROXY-4-{[(7-HYDROXY-6-OXO-2-PHENYL-6,7-DIHYDRO-2H-PYRAZOLO[3,4-B]PYRIDIN-5-YL)AMINO]METHYL}-6-METHYLPYRIDIN-3-YL)METHYL+DIHYDROGEN+PHOSPHATE'>0LD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<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>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4geb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4geb OCA], [https://pdbe.org/4geb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4geb RCSB], [https://www.ebi.ac.uk/pdbsum/4geb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4geb ProSAT]</span></td></tr>
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<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=4geb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4geb OCA], [http://pdbe.org/4geb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4geb RCSB], [http://www.ebi.ac.uk/pdbsum/4geb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4geb ProSAT]</span></td></tr>
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</table>
</table>
== Function ==
== Function ==
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[[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>
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[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The structure-based design, synthesis, and biological evaluation of a new pyrazole series of irreversible KAT II inhibitors are described herein. The modification of the inhibitor scaffold of 1 and 2 from a dihydroquinolinone core to a tetrahydropyrazolopyridinone core led to discovery of a new series of potent KAT II inhibitors with excellent physicochemical properties. Compound 20 is the most potent and lipophilically efficient of these new pyrazole analogs, with a kinact/Ki value of 112,000M(-1)s(-1) and lipophilic efficiency (LipE) of 8.53. The X-ray crystal structure of 20 with KAT II demonstrates key features that contribute to this remarkable potency and binding efficiency.
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PF-04859989 as a template for structure-based drug design: Identification of new pyrazole series of irreversible KAT II inhibitors with improved lipophilic efficiency.,Dounay AB, Anderson M, Bechle BM, Evrard E, Gan X, Kim JY, McAllister LA, Pandit J, Rong S, Salafia MA, Tuttle JB, Zawadzke LE, Verhoest PR Bioorg Med Chem Lett. 2013 Apr 1;23(7):1961-6. doi: 10.1016/j.bmcl.2013.02.039., Epub 2013 Feb 15. PMID:23466229<ref>PMID:23466229</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4geb" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
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[[Category: Pandit, J]]
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[[Category: Large Structures]]
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[[Category: Aminotransferase]]
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[[Category: Pandit J]]
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[[Category: Irreversible inhibitor]]
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[[Category: Transferase-transferase inhibitor complex]]
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Current revision

Kynurenine Aminotransferase II Inhibitors

PDB ID 4geb

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