3coh

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[[Image:3coh.png|left|200px]]
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==Crystal structure of Aurora-A in complex with a pentacyclic inhibitor==
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<StructureSection load='3coh' size='340' side='right' caption='[[3coh]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3coh]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3COH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3COH 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=83H:8-ETHYL-3,10,10-TRIMETHYL-4,5,6,8,10,12-HEXAHYDROPYRAZOLO[4,3 6,7]CYCLOHEPTA[1,2-B]PYRROLO[2,3-F]INDOL-9(1H)-ONE'>83H</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AURKA, AIK, ARK1, AURA, BTAK, STK15, STK6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=3coh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3coh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3coh RCSB], [http://www.ebi.ac.uk/pdbsum/3coh PDBsum]</span></td></tr>
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</table>
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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/co/3coh_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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/chain_selection.php?pdb_ID=2ata 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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Aurora kinase inhibitors have attracted a great deal of interest as a new class of antimitotic agents. We report a novel class of Aurora inhibitors based on a pentacyclic scaffold. A prototype pentacyclic inhibitor 32 (AKI-001) derived from two early lead structures improves upon the best properties of each parent and compares favorably to a previously reported Aurora inhibitor, 39 (VX-680). The inhibitor exhibits low nanomolar potency against both Aurora A and Aurora B enzymes, excellent cellular potency (IC50 &lt; 100 nM), and good oral bioavailability. Phenotypic cellular assays show that both Aurora A and Aurora B are inhibited at inhibitor concentrations sufficient to block proliferation. Importantly, the cellular activity translates to potent inhibition of tumor growth in vivo. An oral dose of 5 mg/kg QD is well tolerated and results in near stasis (92% TGI) in an HCT116 mouse xenograft model.
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{{STRUCTURE_3coh| PDB=3coh | SCENE= }}
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A pentacyclic aurora kinase inhibitor (AKI-001) with high in vivo potency and oral bioavailability.,Rawson TE, Ruth M, Blackwood E, Burdick D, Corson L, Dotson J, Drummond J, Fields C, Georges GJ, Goller B, Halladay J, Hunsaker T, Kleinheinz T, Krell HW, Li J, Liang J, Limberg A, McNutt A, Moffat J, Phillips G, Ran Y, Safina B, Ultsch M, Walker L, Wiesmann C, Zhang B, Zhou A, Zhu BY, Ruger P, Cochran AG J Med Chem. 2008 Aug 14;51(15):4465-75. Epub 2008 Jul 17. PMID:18630890<ref>PMID:18630890</ref>
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===Crystal structure of Aurora-A in complex with a pentacyclic inhibitor===
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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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{{ABSTRACT_PUBMED_18630890}}
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==See Also==
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*[[Serine/threonine protein kinase|Serine/threonine protein kinase]]
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==About this Structure==
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== References ==
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[[3coh]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3COH OCA].
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<references/>
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__TOC__
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==Reference==
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</StructureSection>
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<ref group="xtra">PMID:018630890</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Non-specific serine/threonine protein kinase]]

Revision as of 09:32, 5 November 2014

Crystal structure of Aurora-A in complex with a pentacyclic inhibitor

3coh, resolution 2.70Å

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