2vrx | pdb_00002vrx

Structure of Aurora B kinase in complex with ZM447439

spinqualitylabelsall models 2vrx, resolution 1.86Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2vrx is a 4 chain structure with sequence from Xenopus laevis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.86Å Ligands: 447, TPO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Centromere protein 3D structure Serine/threonine protein kinase 3D structures

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