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| | == Structural highlights == | | == Structural highlights == |
| | <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> | | <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> |
| - | </td></tr><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></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.86Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> | + | <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> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2bfx|2bfx]], [[2vgo|2vgo]], [[2vgp|2vgp]], [[2bfy|2bfy]]</div></td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></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=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> | | <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> |
| | </table> | | </table> |
| | == Function == | | == 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> [[https://www.uniprot.org/uniprot/INCEA_XENLA INCEA_XENLA]] 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.<ref>PMID:12221116</ref> <ref>PMID:17199039</ref>
| + | [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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vr/2vrx_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vr/2vrx_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Non-specific serine/threonine protein kinase]] | |
| | [[Category: Xenopus laevis]] | | [[Category: Xenopus laevis]] |
| - | [[Category: Girdler, F]] | + | [[Category: Girdler F]] |
| - | [[Category: Musacchio, A]] | + | [[Category: Musacchio A]] |
| - | [[Category: Patercoli, S]] | + | [[Category: Patercoli S]] |
| - | [[Category: Ridgway, E]] | + | [[Category: Ridgway E]] |
| - | [[Category: Sessa, F]] | + | [[Category: Sessa F]] |
| - | [[Category: Taylor, S S]] | + | [[Category: Taylor SS]] |
| - | [[Category: Villa, F]] | + | [[Category: Villa F]] |
| - | [[Category: Anti-cancer drug target]]
| + | |
| - | [[Category: Atp-binding]]
| + | |
| - | [[Category: Cell cycle-transferase complex]]
| + | |
| - | [[Category: Cell cycle/transferase]]
| + | |
| - | [[Category: Cell division]]
| + | |
| - | [[Category: Centromere]]
| + | |
| - | [[Category: Coiled coil]]
| + | |
| - | [[Category: Kinase]]
| + | |
| - | [[Category: Magnesium]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Microtubule]]
| + | |
| - | [[Category: Mitosis]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Protein kinase]]
| + | |
| - | [[Category: Serine/threonine-protein kinase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
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.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
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[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bolton MA, Lan W, Powers SE, McCleland ML, Kuang J, Stukenberg PT. Aurora B kinase exists in a complex with survivin and INCENP and its kinase activity is stimulated by survivin binding and phosphorylation. Mol Biol Cell. 2002 Sep;13(9):3064-77. PMID:12221116 doi:10.1091/mbc.E02-02-0092
- ↑ Murnion ME, Adams RR, Callister DM, Allis CD, Earnshaw WC, Swedlow JR. Chromatin-associated protein phosphatase 1 regulates aurora-B and histone H3 phosphorylation. J Biol Chem. 2001 Jul 13;276(28):26656-65. Epub 2001 May 11. PMID:11350965 doi:10.1074/jbc.M102288200
- ↑ Kelly AE, Sampath SC, Maniar TA, Woo EM, Chait BT, Funabiki H. Chromosomal enrichment and activation of the aurora B pathway are coupled to spatially regulate spindle assembly. Dev Cell. 2007 Jan;12(1):31-43. PMID:17199039 doi:10.1016/j.devcel.2006.11.001
- ↑ Girdler F, Sessa F, Patercoli S, Villa F, Musacchio A, Taylor S. Molecular basis of drug resistance in aurora kinases. Chem Biol. 2008 Jun;15(6):552-62. PMID:18559266 doi:10.1016/j.chembiol.2008.04.013
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