2VRX
Structure of Aurora B kinase in complex with ZM447439
Summary for 2VRX
| Entry DOI | 10.2210/pdb2vrx/pdb |
| Related | 2BFX 2BFY 2VGO 2VGP |
| Descriptor | SERINE/THREONINE-PROTEIN KINASE 12-A, INNER CENTROMERE PROTEIN A, N-(4-{[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-yl]amino}phenyl)benzamide, ... (4 entities in total) |
| Functional Keywords | serine/threonine-protein kinase, kinase, nucleus, mitosis, magnesium, cell cycle/transferase, centromere, microtubule, atp-binding, transferase, anti-cancer drug target, phosphoprotein, protein kinase, nucleotide-binding, coiled coil, cell division, metal-binding, cell cycle-transferase complex |
| Biological source | XENOPUS LAEVIS (AFRICAN CLAWED FROG) More |
| Cellular location | Nucleus: Q6DE08 Chromosome, centromere: O13024 |
| Total number of polymer chains | 4 |
| Total formula weight | 78284.39 |
| Authors | Girdler, F.,Sessa, F.,Patercoli, S.,Villa, F.,Ridgway, E.,Musacchio, A.,Taylor, S.S. (deposition date: 2008-04-16, release date: 2008-07-01, Last modification date: 2024-10-16) |
| Primary citation | Girdler, F.,Sessa, F.,Patercoli, S.,Villa, F.,Musacchio, A.,Taylor, S.S. Molecular Basis of Drug Resistance in Aurora Kinases. Chem.Biol., 15:552-, 2008 Cited by PubMed Abstract: 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. PubMed: 18559266DOI: 10.1016/J.CHEMBIOL.2008.04.013 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.86 Å) |
Structure validation
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