5hne

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==X-RAY CRYSTAL STRUCTURE OF HUMAN MITOCHONDRIAL BRANCHED CHAIN AMINOTRANSFERASE (BCATM) COMPLEXED WITH A 2-ARYL BENZIMIDAZOLE COMPOUND AND AN INTERNAL ALDIMINE LINKED PLP COFACTOR==
==X-RAY CRYSTAL STRUCTURE OF HUMAN MITOCHONDRIAL BRANCHED CHAIN AMINOTRANSFERASE (BCATM) COMPLEXED WITH A 2-ARYL BENZIMIDAZOLE COMPOUND AND AN INTERNAL ALDIMINE LINKED PLP COFACTOR==
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<StructureSection load='5hne' size='340' side='right' caption='[[5hne]], [[Resolution|resolution]] 2.04&Aring;' scene=''>
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<StructureSection load='5hne' size='340' side='right'caption='[[5hne]], [[Resolution|resolution]] 2.04&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5hne]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HNE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HNE FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5hne]] 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=5HNE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HNE 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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EL2:1-[(1R,3S)-3-{[(5-BROMOTHIOPHEN-2-YL)CARBONYL]AMINO}CYCLOHEXYL]-N-METHYL-2-(PYRIDIN-2-YL)-1H-BENZIMIDAZOLE-5-CARBOXAMIDE'>EL2</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</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]] 2.04&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5cr5|5cr5]]</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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EL2:1-[(1R,3S)-3-{[(5-BROMOTHIOPHEN-2-YL)CARBONYL]AMINO}CYCLOHEXYL]-N-METHYL-2-(PYRIDIN-2-YL)-1H-BENZIMIDAZOLE-5-CARBOXAMIDE'>EL2</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Branched-chain-amino-acid_transaminase Branched-chain-amino-acid transaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.6.1.42 2.6.1.42] </span></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=5hne FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hne OCA], [https://pdbe.org/5hne PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hne RCSB], [https://www.ebi.ac.uk/pdbsum/5hne PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hne 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=5hne FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hne OCA], [http://pdbe.org/5hne PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hne RCSB], [http://www.ebi.ac.uk/pdbsum/5hne PDBsum]</span></td></tr>
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</table>
</table>
== Function ==
== Function ==
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[[http://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.
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[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.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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To identify BCATm inhibitors suitable for in vivo study, Encoded Library Technology (ELT) was used to affinity screen a 117 million member benzimidazole based DNA encoded library, which identified an inhibitor series with both biochemical and cellular activities. Subsequent SAR studies led to the discovery of a highly potent and selective compound, 1-(3-(5-bromothiophene-2-carboxamido)cyclohexyl)-N-methyl-2-(pyridin-2-yl)-1H-ben zo[d]imidazole-5-carboxamide (8b) with much improved PK properties. X-ray structure revealed that 8b binds to the active site of BACTm in a unique mode via multiple H-bond and van der Waals interactions. After oral administration, 8b raised mouse blood levels of all three branched chain amino acids as a consequence of BCATm inhibition.
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Discovery and Optimization of Potent, Selective, and in Vivo Efficacious 2-Aryl Benzimidazole BCATm Inhibitors.,Deng H, Zhou J, Sundersingh F, Messer JA, Somers DO, Ajakane M, Arico-Muendel CC, Beljean A, Belyanskaya SL, Bingham R, Blazensky E, Boullay AB, Boursier E, Chai J, Carter P, Chung CW, Daugan A, Ding Y, Herry K, Hobbs C, Humphries E, Kollmann C, Nguyen VL, Nicodeme E, Smith SE, Dodic N, Ancellin N ACS Med Chem Lett. 2016 Feb 8;7(4):379-84. doi: 10.1021/acsmedchemlett.5b00389., eCollection 2016 Apr 14. PMID:27096045<ref>PMID:27096045</ref>
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==See Also==
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*[[Aminotransferase 3D structures|Aminotransferase 3D structures]]
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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 5hne" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Branched-chain-amino-acid transaminase]]
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[[Category: Homo sapiens]]
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[[Category: Somers, D O]]
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[[Category: Large Structures]]
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[[Category: Fold type iv]]
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[[Category: Somers DO]]
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[[Category: Transferase]]
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Current revision

X-RAY CRYSTAL STRUCTURE OF HUMAN MITOCHONDRIAL BRANCHED CHAIN AMINOTRANSFERASE (BCATM) COMPLEXED WITH A 2-ARYL BENZIMIDAZOLE COMPOUND AND AN INTERNAL ALDIMINE LINKED PLP COFACTOR

PDB ID 5hne

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