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[[Image:2vgp.jpg|left|200px]]
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{{STRUCTURE_2vgp|  PDB=2vgp  |  SCENE=  }}
'''CRYSTAL STRUCTURE OF AURORA B KINASE IN COMPLEX WITH A AMINOTHIAZOLE INHIBITOR'''


==Crystal structure of Aurora B kinase in complex with a aminothiazole inhibitor==
<StructureSection load='2vgp' size='340' side='right'caption='[[2vgp]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2vgp]] 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=2VGP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VGP FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AD6:4-[(5-BROMO-1,3-THIAZOL-2-YL)AMINO]-N-METHYLBENZAMIDE'>AD6</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></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=2vgp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vgp OCA], [https://pdbe.org/2vgp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vgp RCSB], [https://www.ebi.ac.uk/pdbsum/2vgp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vgp ProSAT]</span></td></tr>
</table>
== Function ==
[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>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vg/2vgp_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=2vgp ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Aurora family kinases regulate important events during mitosis including centrosome maturation and separation, mitotic spindle assembly, and chromosome segregation. Misregulation of Aurora kinases due to genetic amplification and protein overexpression results in aneuploidy and may contribute to tumorigenesis. Here we report the discovery of new small molecule aminothiazole inhibitors of Aurora kinases with exceptional kinase selectivity and report a 1.7 A cocrystal structure with the Aurora B:INCENP complex from Xenopus laevis. The compounds recapitulate the hallmarks of Aurora kinase inhibition, including decreased histone H3 serine 10 phosphorylation, failure to complete cytokinesis, and endoreduplication.


==Overview==
Discovery of selective aminothiazole aurora kinase inhibitors.,Andersen CB, Wan Y, Chang JW, Riggs B, Lee C, Liu Y, Sessa F, Villa F, Kwiatkowski N, Suzuki M, Nallan L, Heald R, Musacchio A, Gray NS ACS Chem Biol. 2008 Mar 20;3(3):180-92. Epub 2008 Feb 29. PMID:18307303<ref>PMID:18307303</ref>
Aurora family kinases regulate important events during mitosis including centrosome maturation and separation, mitotic spindle assembly, and chromosome segregation. Misregulation of Aurora kinases due to genetic amplification and protein overexpression results in aneuploidy and may contribute to tumorigenesis. Here we report the discovery of new small molecule aminothiazole inhibitors of Aurora kinases with exceptional kinase selectivity and report a 1.7 A cocrystal structure with the Aurora B:INCENP complex from Xenopus laevis. The compounds recapitulate the hallmarks of Aurora kinase inhibition, including decreased histone H3 serine 10 phosphorylation, failure to complete cytokinesis, and endoreduplication.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2VGP is a [[Protein complex]] structure of sequences 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=2VGP OCA].
</div>
<div class="pdbe-citations 2vgp" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Discovery of selective aminothiazole aurora kinase inhibitors., Andersen CB, Wan Y, Chang JW, Riggs B, Lee C, Liu Y, Sessa F, Villa F, Kwiatkowski N, Suzuki M, Nallan L, Heald R, Musacchio A, Gray NS, ACS Chem Biol. 2008 Mar 20;3(3):180-92. Epub 2008 Feb 29. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18307303 18307303]
*[[Centromere protein 3D structure|Centromere protein 3D structure]]
[[Category: Non-specific serine/threonine protein kinase]]
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
[[Category: Protein complex]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Xenopus laevis]]
[[Category: Xenopus laevis]]
[[Category: Andersen, C B.]]
[[Category: Andersen CB]]
[[Category: Chang, J W.]]
[[Category: Chang JW]]
[[Category: Gray, N S.]]
[[Category: Gray NS]]
[[Category: Lee, C.]]
[[Category: Lee C]]
[[Category: Liu, Y.]]
[[Category: Liu Y]]
[[Category: Musacchio, A.]]
[[Category: Musacchio A]]
[[Category: Nallan, L.]]
[[Category: Nallan L]]
[[Category: Sessa, F.]]
[[Category: Sessa F]]
[[Category: Villa, F.]]
[[Category: Villa F]]
[[Category: Wan, Y.]]
[[Category: Wan Y]]
[[Category: Aminothiazole]]
[[Category: Atp-binding]]
[[Category: Aurora b]]
[[Category: Cancer]]
[[Category: Cell cycle]]
[[Category: Cell division]]
[[Category: Centromere]]
[[Category: Coiled coil]]
[[Category: Incenp]]
[[Category: Kinase]]
[[Category: Magnesium]]
[[Category: Metal-binding]]
[[Category: Microtubule]]
[[Category: Mitosis]]
[[Category: Nucleotide-binding]]
[[Category: Nucleus]]
[[Category: Phosphorylation]]
[[Category: Serine/threonine-protein kinase]]
[[Category: Transferase]]
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