2abj

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(New page: 200px<br /> <applet load="2abj" size="450" color="white" frame="true" align="right" spinBox="true" caption="2abj, resolution 2.200&Aring;" /> '''Crystal structure ...)
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[[Image:2abj.gif|left|200px]]<br />
 
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<applet load="2abj" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2abj, resolution 2.200&Aring;" />
 
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'''Crystal structure of human branched chain amino acid transaminase in a complex with an inhibitor, C16H10N2O4F3SCl, and pyridoxal 5' phosphate.'''<br />
 
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==Overview==
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==Crystal structure of human branched chain amino acid transaminase in a complex with an inhibitor, C16H10N2O4F3SCl, and pyridoxal 5' phosphate.==
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The inhibition of the cytosolic isoenzyme BCAT that is expressed, specifically in neuronal tissue is likely to be useful for the treatment, of neurodegenerative and other neurological disorders where glutamatergic, mechanisms are implicated. Compound 2 exhibited an IC50 of 0.8 microM in, the hBCATc assays; it is an active and selective inhibitor. Inhibitor 2, also blocked calcium influx into neuronal cells following inhibition of, glutamate uptake, and demonstrated neuroprotective efficacy in vivo. SAR, pharmacology, and the crystal structure of hBCATc with inhibitor 2 are, described.
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<StructureSection load='2abj' size='340' side='right'caption='[[2abj]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2abj]] is a 4 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=2ABJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ABJ FirstGlance]. <br>
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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]] 2.2&#8491;</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=CBC:N-(5-CHLOROBENZOFURAN-2-CARBONYL)-2-(TRIFLUOROMETHYL)BENZENESULFONOHYDRAZIDE'>CBC</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></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=2abj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2abj OCA], [https://pdbe.org/2abj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2abj RCSB], [https://www.ebi.ac.uk/pdbsum/2abj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2abj ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/BCAT1_HUMAN BCAT1_HUMAN] Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ab/2abj_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2abj ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The inhibition of the cytosolic isoenzyme BCAT that is expressed specifically in neuronal tissue is likely to be useful for the treatment of neurodegenerative and other neurological disorders where glutamatergic mechanisms are implicated. Compound 2 exhibited an IC50 of 0.8 microM in the hBCATc assays; it is an active and selective inhibitor. Inhibitor 2 also blocked calcium influx into neuronal cells following inhibition of glutamate uptake, and demonstrated neuroprotective efficacy in vivo. SAR, pharmacology, and the crystal structure of hBCATc with inhibitor 2 are described.
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==Disease==
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The design and synthesis of human branched-chain amino acid aminotransferase inhibitors for treatment of neurodegenerative diseases.,Hu LY, Boxer PA, Kesten SR, Lei HJ, Wustrow DJ, Moreland DW, Zhang L, Ahn K, Ryder TR, Liu X, Rubin JR, Fahnoe K, Carroll RT, Dutta S, Fahnoe DC, Probert AW, Roof RL, Rafferty MF, Kostlan CR, Scholten JD, Hood M, Ren XD, Schielke GP, Su TZ, Taylor CP, Mistry A, McConnell P, Hasemann C, Ohren J Bioorg Med Chem Lett. 2006 May 1;16(9):2337-40. Epub 2005 Sep 6. PMID:16143519<ref>PMID:16143519</ref>
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Known diseases associated with this structure: Hyperleucinemia-isoleucinemia or hypervalinemia (1) OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=113520 113520]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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2ABJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CBC and PLP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2ABJ OCA].
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</div>
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<div class="pdbe-citations 2abj" style="background-color:#fffaf0;"></div>
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==Reference==
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== References ==
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The design and synthesis of human branched-chain amino acid aminotransferase inhibitors for treatment of neurodegenerative diseases., Hu LY, Boxer PA, Kesten SR, Lei HJ, Wustrow DJ, Moreland DW, Zhang L, Ahn K, Ryder TR, Liu X, Rubin JR, Fahnoe K, Carroll RT, Dutta S, Fahnoe DC, Probert AW, Roof RL, Rafferty MF, Kostlan CR, Scholten JD, Hood M, Ren XD, Schielke GP, Su TZ, Taylor CP, Mistry A, McConnell P, Hasemann C, Ohren J, Bioorg Med Chem Lett. 2006 May 1;16(9):2337-40. Epub 2005 Sep 6. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16143519 16143519]
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<references/>
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[[Category: Branched-chain-amino-acid transaminase]]
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Hasemann, C.H.]]
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[[Category: Hasemann CH]]
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[[Category: Hu, H.L.]]
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[[Category: Hu HL]]
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[[Category: McConnell, P.C.]]
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[[Category: McConnell PC]]
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[[Category: Mistry, A.]]
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[[Category: Mistry A]]
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[[Category: Moreland, D.W.]]
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[[Category: Moreland DW]]
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[[Category: Mueller, W.T.]]
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[[Category: Mueller WT]]
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[[Category: Ohren, J.F.]]
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[[Category: Ohren JF]]
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[[Category: Rubin, J.R.]]
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[[Category: Rubin JR]]
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[[Category: Scholten, J.D.]]
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[[Category: Scholten JD]]
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[[Category: CBC]]
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[[Category: PLP]]
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[[Category: branched-chain-amino-acid aminotransferase]]
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[[Category: cytosolic]]
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[[Category: inhibitor-bound]]
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[[Category: plp-lys220 schiff base]]
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[[Category: pyridoxal-phosphate-dependent aminotransferase]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:48:30 2007''
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Current revision

Crystal structure of human branched chain amino acid transaminase in a complex with an inhibitor, C16H10N2O4F3SCl, and pyridoxal 5' phosphate.

PDB ID 2abj

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