4af3

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[[Image:4af3.png|left|200px]]
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==Human Aurora B Kinase in complex with INCENP and VX-680==
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<StructureSection load='4af3' size='340' side='right' caption='[[4af3]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4af3]] 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=4AF3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AF3 FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=VX6:CYCLOPROPANECARBOXYLIC+ACID+{4-[4-(4-METHYL-PIPERAZIN-1-YL)-6-(5-METHYL-2H-PYRAZOL-3-YLAMINO)-PYRIMIDIN-2-YLSULFANYL]-PHENYL}-AMIDE'>VX6</scene><br>
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<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4af3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4af3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4af3 RCSB], [http://www.ebi.ac.uk/pdbsum/4af3 PDBsum]</span></td></tr>
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<table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/AURKB_HUMAN AURKB_HUMAN]] Disruptive regulation of expression is a possible mechanism of the perturbation of chromosomal integrity in cancer cells through its dominant-negative effect on cytokinesis.
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== Function ==
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[[http://www.uniprot.org/uniprot/AURKB_HUMAN AURKB_HUMAN]] 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. AURKB phosphorylates the CPC complex subunits BIRC5/survivin, CDCA8/borealin and INCENP. Phosphorylation of INCENP leads to increased AURKB activity. Other known AURKB substrates involved in centromeric functions and mitosis are CENPA, DES/desmin, GPAF, KIF2C, NSUN2, RACGAP1, SEPT1, VIM/vimentin, GSG2/Haspin, and histone H3. A positive feedback loop involving GSG2 and AURKB contributes to localization of CPC to centromeres. Phosphorylation of VIM controls vimentin filament segregation in cytokinetic process, whereas histone H3 is phosphorylated at 'Ser-10' and 'Ser-28' during mitosis (H3S10ph and H3S28ph, respectively). A positive feedback between GSG2 and AURKB contributes to CPC localization. AURKB is also required for kinetochore localization of BUB1 and SGOL1. Phosphorylation of p53/TP53 negatively regulates its transcriptional activity. Key regulator of active promoters in resting B- and T-lymphocytes: acts by mediating phosphorylation of H3S28ph at active promoters in resting B-cells, inhibiting RNF2/RING1B-mediated ubiquitination of histone H2A and enhancing binding and activity of the USP16 deubiquitinase at transcribed genes.<ref>PMID:11516652</ref> <ref>PMID:11756469</ref> <ref>PMID:11856369</ref> <ref>PMID:11784863</ref> <ref>PMID:12689593</ref> <ref>PMID:12458200</ref> <ref>PMID:12686604</ref> <ref>PMID:12925766</ref> <ref>PMID:14610074</ref> <ref>PMID:14722118</ref> <ref>PMID:15020684</ref> <ref>PMID:15249581</ref> <ref>PMID:14602875</ref> <ref>PMID:16103226</ref> <ref>PMID:17617734</ref> <ref>PMID:21658950</ref> <ref>PMID:20959462</ref> [[http://www.uniprot.org/uniprot/INCE_HUMAN INCE_HUMAN]] 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. Probably acts through association with AURKB or AURKC. Seems to bind directly to microtubules. Controls the kinetochore localization of BUB1.<ref>PMID:15316025</ref> <ref>PMID:12925766</ref> <ref>PMID:16760428</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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We present the structure of the human Aurora B kinase domain in complex with the C-terminal Aurora-binding region of human INCENP and the Aurora kinase inhibitor VX-680. The structure unexpectedly reveals a dimeric arrangement of the Aurora B:INCENP complex, which was confirmed to exist in solution by analytical ultracentrifugation. The dimerization involves a domain swap of the activation loop, resulting in a different conformation of the DFG motif as compared to that seen in other kinase complexes with VX-680. The binding of INCENP differs significantly from that seen in the Xenopus laevis Aurora B:INCENP complex currently used as a model for structure-based design for this important oncology target.
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{{STRUCTURE_4af3| PDB=4af3 | SCENE= }}
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Crystal Structure of Human Aurora B in Complex with INCENP and VX-680.,Elkins JM, Santaguida S, Musacchio A, Knapp S J Med Chem. 2012 Sep 13;55(17):7841-8. Epub 2012 Sep 4. PMID:22920039<ref>PMID:22920039</ref>
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===Human Aurora B Kinase in complex with INCENP and VX-680===
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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_22920039}}
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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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[[4af3]] 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=4AF3 OCA].
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Non-specific serine/threonine protein kinase]]

Revision as of 09:07, 2 July 2014

Human Aurora B Kinase in complex with INCENP and VX-680

4af3, resolution 2.75Å

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