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| | <StructureSection load='5i5y' size='340' side='right'caption='[[5i5y]], [[Resolution|resolution]] 1.81Å' scene=''> | | <StructureSection load='5i5y' size='340' side='right'caption='[[5i5y]], [[Resolution|resolution]] 1.81Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5i5y]] 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=5I5Y OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5I5Y FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5i5y]] 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=5I5Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5I5Y FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=68D:{2-[(5-METHYL-4-OXO-3,4-DIHYDROTHIENO[2,3-D]PYRIMIDINE-6-CARBONYL)AMINO]PHENYL}ACETIC+ACID'>68D</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.81Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5i5s|5i5s]], [[5i5t|5i5t]], [[5i5u|5i5u]], [[5i5v|5i5v]], [[5i5w|5i5w]], [[5i5x|5i5x]], [[5i60|5i60]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=68D:{2-[(5-METHYL-4-OXO-3,4-DIHYDROTHIENO[2,3-D]PYRIMIDINE-6-CARBONYL)AMINO]PHENYL}ACETIC+ACID'>68D</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BCAT2, BCATM, BCT2, ECA40 ([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=5i5y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i5y OCA], [https://pdbe.org/5i5y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5i5y RCSB], [https://www.ebi.ac.uk/pdbsum/5i5y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5i5y ProSAT]</span></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'>[http://proteopedia.org/fgij/fg.htm?mol=5i5y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i5y OCA], [http://pdbe.org/5i5y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i5y RCSB], [http://www.ebi.ac.uk/pdbsum/5i5y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5i5y ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == 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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Branched-chain-amino-acid transaminase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Somers, D O]] | + | [[Category: Somers DO]] |
| - | [[Category: Fold type iv]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
5i5y is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.81Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
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.
Publication Abstract from PubMed
Inhibitors of mitochondrial branched chain aminotransferase (BCATm), identified using fragment screening, are described. This was carried out using a combination of STD-NMR, thermal melt (Tm), and biochemical assays to identify compounds that bound to BCATm, which were subsequently progressed to X-ray crystallography, where a number of exemplars showed significant diversity in their binding modes. The hits identified were supplemented by searching and screening of additional analogues, which enabled the gathering of further X-ray data where the original hits had not produced liganded structures. The fragment hits were optimized using structure-based design, with some transfer of information between series, which enabled the identification of ligand efficient lead molecules with micromolar levels of inhibition, cellular activity, and good solubility.
Structurally Diverse Mitochondrial Branched Chain Aminotransferase (BCATm) Leads with Varying Binding Modes Identified by Fragment Screening.,Borthwick JA, Ancellin N, Bertrand SM, Bingham RP, Carter PS, Chung CW, Churcher I, Dodic N, Fournier C, Francis PL, Hobbs A, Jamieson C, Pickett SD, Smith SE, Somers DO, Spitzfaden C, Suckling CJ, Young RJ J Med Chem. 2016 Mar 24;59(6):2452-67. doi: 10.1021/acs.jmedchem.5b01607. Epub, 2016 Mar 16. PMID:26938474[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Borthwick JA, Ancellin N, Bertrand SM, Bingham RP, Carter PS, Chung CW, Churcher I, Dodic N, Fournier C, Francis PL, Hobbs A, Jamieson C, Pickett SD, Smith SE, Somers DO, Spitzfaden C, Suckling CJ, Young RJ. Structurally Diverse Mitochondrial Branched Chain Aminotransferase (BCATm) Leads with Varying Binding Modes Identified by Fragment Screening. J Med Chem. 2016 Mar 24;59(6):2452-67. doi: 10.1021/acs.jmedchem.5b01607. Epub, 2016 Mar 16. PMID:26938474 doi:http://dx.doi.org/10.1021/acs.jmedchem.5b01607
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