3ztx

Aurora kinase selective inhibitors identified using a Taxol-induced checkpoint sensitivity screen.

spinqualitylabelsall models 3ztx, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3ztx is a 4 chain structure with sequence from African clawed frog. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ZTX NonStd Res: TPO Related: 2bfx, 2vgo, 2vrx, 2vgp, 2bfy Activity: Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 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. [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. Publication Abstract from PubMed The members of the Aurora kinase family play critical roles in the regulation of the cell cycle and mitotic spindle assembly and have been intensively investigated as potential targets for a new class of anticancer drugs. We describe a new highly potent and selective class of Aurora kinase inhibitors discovered using a phenotypic cellular screen. Optimized inhibitors display many of the hallmarks of Aurora inhibition including endoreduplication, polyploidy, and loss of cell viability in cancer cells. Structure-activity relationships with respect to kinome-wide selectivity and guided by an Aurora B co-crystal structure resulted in the identification of key selectivity determinants and discovery of a subseries with selectivity toward Aurora A. A direct comparison of biochemical and cellular profiles with respect to published Aurora inhibitors including VX-680, AZD1152, MLN8054, and a pyrimidine-based compound from Genentech demonstrates that compounds 1 and 3 will become valuable additional pharmacological probes of Aurora-dependent functions. Selective aurora kinase inhibitors identified using a taxol-induced checkpoint sensitivity screen.,Kwiatkowski N, Deng X, Wang J, Tan L, Villa F, Santaguida S, Huang HC, Mitchison T, Musacchio A, Gray N ACS Chem Biol. 2012 Jan 20;7(1):185-96. Epub 2011 Oct 21. PMID:21992004 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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