2vrx

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[[Image:2vrx.png|left|200px]]
 
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{{STRUCTURE_2vrx| PDB=2vrx | SCENE= }}
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==Structure of Aurora B kinase in complex with ZM447439==
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<StructureSection load='2vrx' size='340' side='right'caption='[[2vrx]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2vrx]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VRX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VRX 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]] 1.86&#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=447:N-(4-{[6-METHOXY-7-(3-MORPHOLIN-4-YLPROPOXY)QUINAZOLIN-4-YL]AMINO}PHENYL)BENZAMIDE'>447</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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=2vrx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vrx OCA], [https://pdbe.org/2vrx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vrx RCSB], [https://www.ebi.ac.uk/pdbsum/2vrx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vrx ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/AUKBA_XENLA AUKBA_XENLA] Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Involved in the bipolar attachment of spindle microtubules to kinetochores and is a key regulator for the onset of cytokinesis during mitosis. Required for central/midzone spindle assembly and cleavage furrow formation. Phosphorylates 'Ser-10' of histone H3 during mitosis.<ref>PMID:12221116</ref> <ref>PMID:11350965</ref> <ref>PMID:17199039</ref>
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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/vr/2vrx_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=2vrx 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 kinases have emerged as potential targets in cancer therapy, and several drugs are currently undergoing preclinical and clinical validation. Whether clinical resistance to these drugs can arise is unclear. We exploited a hypermutagenic cancer cell line to select mutations conferring resistance to a well-studied Aurora inhibitor, ZM447439. All resistant clones contained dominant point mutations in Aurora B. Three mutations map to residues in the ATP-binding pocket that are distinct from the "gatekeeper" residue. The mutants retain wild-type catalytic activity and were resistant to all of the Aurora inhibitors tested. Our studies predict that drug-resistant Aurora B mutants are likely to arise during clinical treatment. Furthermore, because the plasticity of the ATP-binding pocket renders Aurora B insensitive to multiple inhibitors, our observations indicate that the drug-resistant Aurora B mutants should be exploited as novel drug targets.
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===STRUCTURE OF AURORA B KINASE IN COMPLEX WITH ZM447439===
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Molecular basis of drug resistance in aurora kinases.,Girdler F, Sessa F, Patercoli S, Villa F, Musacchio A, Taylor S Chem Biol. 2008 Jun;15(6):552-62. PMID:18559266<ref>PMID:18559266</ref>
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{{ABSTRACT_PUBMED_18559266}}
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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 2vrx" style="background-color:#fffaf0;"></div>
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==About this Structure==
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==See Also==
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[[2vrx]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VRX OCA].
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*[[Centromere protein 3D structure|Centromere protein 3D structure]]
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*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
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==Reference==
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== References ==
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<ref group="xtra">PMID:018559266</ref><references group="xtra"/>
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<references/>
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[[Category: Non-specific serine/threonine protein kinase]]
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Xenopus laevis]]
[[Category: Xenopus laevis]]
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[[Category: Girdler, F.]]
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[[Category: Girdler F]]
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[[Category: Musacchio, A.]]
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[[Category: Musacchio A]]
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[[Category: Patercoli, S.]]
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[[Category: Patercoli S]]
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[[Category: Ridgway, E.]]
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[[Category: Ridgway E]]
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[[Category: Sessa, F.]]
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[[Category: Sessa F]]
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[[Category: Taylor, S S.]]
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[[Category: Taylor SS]]
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[[Category: Villa, F.]]
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[[Category: Villa F]]
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[[Category: Anti-cancer drug target]]
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[[Category: Atp-binding]]
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[[Category: Cell cycle-transferase complex]]
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[[Category: Cell cycle/transferase]]
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[[Category: Cell division]]
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[[Category: Centromere]]
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[[Category: Kinase]]
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[[Category: Magnesium]]
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[[Category: Metal-binding]]
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[[Category: Microtubule]]
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[[Category: Mitosis]]
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[[Category: Nucleotide-binding]]
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[[Category: Nucleus]]
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[[Category: Phosphoprotein]]
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[[Category: Protein kinase]]
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[[Category: Serine/threonine-protein kinase]]
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[[Category: Transferase]]
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Current revision

Structure of Aurora B kinase in complex with ZM447439

PDB ID 2vrx

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Proteopedia Page Contributors and Editors (what is this?)

OCA

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