2vrx
From Proteopedia
Structure of Aurora B kinase in complex with ZM447439
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] [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.[4] [5] 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 PubMedAurora 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[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Large Structures | Non-specific serine/threonine protein kinase | Xenopus laevis | Girdler, F | Musacchio, A | Patercoli, S | Ridgway, E | Sessa, F | Taylor, S S | Villa, F | Anti-cancer drug target | Atp-binding | Cell cycle-transferase complex | Cell cycle/transferase | Cell division | Centromere | Coiled coil | Kinase | Magnesium | Metal-binding | Microtubule | Mitosis | Nucleotide-binding | Nucleus | Phosphoprotein | Protein kinase | Serine/threonine-protein kinase | Transferase
