2vrx

STRUCTURE OF AURORA B KINASE IN COMPLEX WITH ZM447439STRUCTURE OF AURORA B KINASE IN COMPLEX WITH ZM447439

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. Ligands: NonStd Res: Related: 2bfx, 2vgo, 2vgp, 2bfy Activity: Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Resources: FirstGlance, OCA, RCSB, PDBsum 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 Serine/threonine protein kinase

spinqualitylabelsall models 2vrx, resolution 1.86Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image