5cr5: Difference between revisions

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 ==X-RAY CRYSTAL STRUCTURE AT 1.61A RESOLUTION OF HUMAN MITOCHONDRIAL BRANCHED CHAIN AMINOTRANSFERASE (BCATM) COMPLEXED WITH A BIPHENYL PYRROLIDINE ETHER COMPOUND AND AN INTERNAL ALDIMINE LINKED PLP COFACTOR.==
-<StructureSection load='5cr5' size='340' side='right' caption='[[5cr5]], [[Resolution|resolution]] 1.61&Aring;' scene=''>
+<StructureSection load='5cr5' size='340' side='right'caption='[[5cr5]], [[Resolution|resolution]] 1.61&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5cr5]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CR5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CR5 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5cr5]] 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=5CR5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CR5 FirstGlance]. <br>
-</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=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EL1:3-({(3R)-1-[(5-BROMOTHIOPHEN-2-YL)CARBONYL]PYRROLIDIN-3-YL}OXY)-N-METHYL-2-[(METHYLSULFONYL)AMINO]BIPHENYL-4-CARBOXAMIDE'>EL1</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr>
+</td></tr><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=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EL1:3-({(3R)-1-[(5-BROMOTHIOPHEN-2-YL)CARBONYL]PYRROLIDIN-3-YL}OXY)-N-METHYL-2-[(METHYLSULFONYL)AMINO]BIPHENYL-4-CARBOXAMIDE'>EL1</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr>
-<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>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5cr5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cr5 OCA], [https://pdbe.org/5cr5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5cr5 RCSB], [https://www.ebi.ac.uk/pdbsum/5cr5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5cr5 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=5cr5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cr5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=5cr5 RCSB], [http://www.ebi.ac.uk/pdbsum/5cr5 PDBsum]</span></td></tr>
 </table>
 == Function ==
-[[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.
+[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 ==
+As a potential target for obesity, human BCATm was screened against more than 14 billion DNA encoded compounds of distinct scaffolds followed by off-DNA synthesis and activity confirmation. As a consequence, several series of BCATm inhibitors were discovered. One representative compound (R)-3-((1-(5-bromothiophene-2-carbonyl)pyrrolidin-3-yl)oxy)-N-methyl-2'-(methylsu lfonamido)-[1,1'-biphenyl]-4-carboxamide (15e) from a novel compound library synthesized via on-DNA Suzuki-Miyaura cross-coupling showed BCATm inhibitory activity with IC50 = 2.0 muM. A protein crystal structure of 15e revealed that it binds to BCATm within the catalytic site adjacent to the PLP cofactor. The identification of this novel inhibitor series plus the establishment of a BCATm protein structure provided a good starting point for future structure-based discovery of BCATm inhibitors.
+Discovery, SAR, and X-ray Binding Mode Study of BCATm Inhibitors from a Novel DNA-Encoded Library.,Deng H, Zhou J, Sundersingh FS, Summerfield J, Somers D, Messer JA, Satz AL, Ancellin N, Arico-Muendel CC, Sargent Bedard KL, Beljean A, Belyanskaya SL, Bingham R, Smith SE, Boursier E, Carter P, Centrella PA, Clark MA, Chung CW, Davie CP, Delorey JL, Ding Y, Franklin GJ, Grady LC, Herry K, Hobbs C, Kollmann CS, Morgan BA, Pothier Kaushansky LJ, Zhou Q ACS Med Chem Lett. 2015 Jul 21;6(8):919-24. doi: 10.1021/acsmedchemlett.5b00179. , eCollection 2015 Aug 13. PMID:26288694<ref>PMID:26288694</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 5cr5" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Aminotransferase 3D structures|Aminotransferase 3D structures]]
+== References ==
+<references/>
 __TOC__
 </StructureSection>
-[[Category: Branched-chain-amino-acid transaminase]]
+[[Category: Homo sapiens]]
-[[Category: Somers, D O]]
+[[Category: Large Structures]]
-[[Category: Fold type iv]]
+[[Category: Somers DO]]
-[[Category: Transferase]]