2vgp

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[[Image:2vgp.jpg|left|200px]]
 
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{{Structure
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==Crystal structure of Aurora B kinase in complex with a aminothiazole inhibitor==
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|PDB= 2vgp |SIZE=350|CAPTION= <scene name='initialview01'>2vgp</scene>, resolution 1.70&Aring;
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<StructureSection load='2vgp' size='340' side='right'caption='[[2vgp]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
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|SITE= <scene name='pdbsite=AC1:Ad6+Binding+Site+For+Chain+A'>AC1</scene> and <scene name='pdbsite=AC2:Ad6+Binding+Site+For+Chain+B'>AC2</scene>
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=AD6:4-[(5-BROMO-1,3-THIAZOL-2-YL)AMINO]-N-METHYLBENZAMIDE'>AD6</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene>
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<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>
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|ACTIVITY= <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>
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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]] 1.7&#8491;</td></tr>
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|GENE=
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<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>
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|DOMAIN=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=smart00220 S_TKc], [http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=cd00180 S_TKc], [http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=pfam03941 INCENP_ARK-bind]</span>
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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=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>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2vgp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vgp OCA], [http://www.ebi.ac.uk/pdbsum/2vgp PDBsum], [http://www.fli-leibniz.de/cgi-bin/ImgLib.pl?CODE=1kfv JenaLib], [http://www.rcsb.org/pdb/explore.do?structureId=2vgp RCSB]</span>
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</table>
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}}
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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/vg/2vgp_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/main_output.php?pdb_ID=2vgp 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 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.
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'''CRYSTAL STRUCTURE OF AURORA B KINASE IN COMPLEX WITH A AMINOTHIAZOLE INHIBITOR'''
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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>
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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 2vgp" style="background-color:#fffaf0;"></div>
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==Overview==
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==See Also==
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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.
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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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==About this Structure==
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== References ==
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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].
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<references/>
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__TOC__
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==Reference==
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</StructureSection>
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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]
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[[Category: Large Structures]]
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[[Category: Non-specific serine/threonine protein kinase]]
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[[Category: Protein complex]]
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[[Category: Xenopus laevis]]
[[Category: Xenopus laevis]]
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[[Category: Andersen, C B.]]
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[[Category: Andersen CB]]
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[[Category: Chang, J W.]]
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[[Category: Chang JW]]
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[[Category: Gray, N S.]]
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[[Category: Gray NS]]
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[[Category: Lee, C.]]
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[[Category: Lee C]]
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[[Category: Liu, Y.]]
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[[Category: Liu Y]]
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[[Category: Musacchio, A.]]
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[[Category: Musacchio A]]
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[[Category: Nallan, L.]]
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[[Category: Nallan L]]
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[[Category: Sessa, F.]]
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[[Category: Sessa F]]
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[[Category: Villa, F.]]
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[[Category: Villa F]]
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[[Category: Wan, Y.]]
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[[Category: Wan Y]]
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[[Category: aminothiazole]]
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[[Category: atp-binding]]
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[[Category: aurora b]]
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[[Category: cancer]]
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[[Category: cell cycle]]
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[[Category: cell division]]
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[[Category: centromere]]
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[[Category: coiled coil]]
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[[Category: incenp]]
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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: phosphorylation]]
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[[Category: serine/threonine-protein kinase]]
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[[Category: transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Mar 26 10:03:14 2008''
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Current revision

Crystal structure of Aurora B kinase in complex with a aminothiazole inhibitor

PDB ID 2vgp

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