5bww: Difference between revisions

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OCA

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-'''Unreleased structure'''
-The entry 5bww is ON HOLD
+==X-RAY CRYSTAL STRUCTURE AT 1.82A RESOLUTION OF HUMAN MITOCHONDRIAL BRANCHED CHAIN AMINOTRANSFERASE (BCATM) COMPLEXED WITH A PYRROLIDINE AMIDE COMPOUND AND AN INTERNAL ALDIMINE LINKED PLP COFACTOR.==
+<StructureSection load='5bww' size='340' side='right'caption='[[5bww]], [[Resolution|resolution]] 1.82&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5bww]] 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=5BWW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BWW FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4W6:7-OXO-2-[2-OXO-2-(PYRROLIDIN-1-YL)ETHYL]-5-PROPYL-4,7-DIHYDROPYRAZOLO[1,5-A]PYRIMIDINE-3-CARBONITRILE'>4W6</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</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=5bww FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bww OCA], [https://pdbe.org/5bww PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bww RCSB], [https://www.ebi.ac.uk/pdbsum/5bww PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bww ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/BCAT2_HUMAN BCAT2_HUMAN] Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine. May also function as a transporter of branched chain alpha-keto acids.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The hybridisation of hits, identified by complementary fragment and high throughput screens, enabled the discovery of the first series of potent inhibitors of mitochondrial branched-chain aminotransferase (BCATm), based on a 2-benzylamino-pyrazolo[1,5-a]pyrimidinone-3-carbonitrile template. Structure-guided growth enabled rapid optimisation of activity with maintenance of ligand efficiency, whilst the focus on physical properties delivered compounds with excellent pharmacokinetic exposure that enabled an acute proof of concept experiment in mice. Oral administration of 2-((4-chloro-2,6-difluorobenzyl)amino)-7-oxo-5-propyl-4,7-dihydropyrazolo[1,5-a]p yrimidine-3-carbonitrile 61 significantly raised the circulating levels of the branched-chain amino acids leucine, isoleucine and valine in this acute study.
-Authors: SOMERS, D.O.
+The discovery of in vivo active mitochondrial branched-chain aminotransferase (BCATm) inhibitors by hybridising fragment and HTS hits.,Bertrand SM, Ancellin N, Beaufils B, Bingham RP, Borthwick JA, Boullay AB, Boursier E, Carter PS, Chung CW, Churcher I, Dodic N, Fouchet MH, Fournier C, Francis P, Gummer LA, Herry K, Hobbs A, Hobbs CI, Homes P, Jamieson C, Nicodeme E, Pickett SD, Reid IH, Simpson GL, Sloan LA, Smith SE, Somers DO, Spitzfaden C, Suckling CJ, Valko K, Washio Y, Young RJ J Med Chem. 2015 Jun 19. PMID:26090771<ref>PMID:26090771</ref>
-Description: X-RAY CRYSTAL STRUCTURE AT 1.82A RESOLUTION OF HUMAN MITOCHONDRIAL BRANCHED CHAIN AMINOTRANSFERASE (BCATM) COMPLEXED WITH A PYRROLIDINE AMIDE COMPOUND AND AN INTERNAL ALDIMINE LINKED PLP COFACTOR.
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Somers, D.O]]
+<div class="pdbe-citations 5bww" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Aminotransferase 3D structures|Aminotransferase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Somers DO]]