2VGP

Crystal structure of Aurora B kinase in complex with a aminothiazole inhibitor

Summary for 2VGP

• Entry DOI: 10.2210/pdb2vgp/pdb
• Related: 2BFX 2BFY 2VGO
• Descriptor: SERINE/THREONINE-PROTEIN KINASE 12-A, INNER CENTROMERE PROTEIN A, 4-[(5-bromo-1,3-thiazol-2-yl)amino]-N-methylbenzamide, ... (4 entities in total)
• Functional Keywords: nucleotide-binding, serine/threonine-protein kinase, atp-binding, transferase, coiled coil, cell division, kinase, cancer, incenp, nucleus, mitosis, aurora b, metal-binding, aminothiazole, phosphorylation, magnesium, cell cycle, centromere, microtubule
• Biological source: XENOPUS LAEVIS (AFRICAN CLAWED FROG); More
• Cellular location: Nucleus: Q6DE08; Chromosome, centromere: O13024
• Total number of polymer chains: 4
• Total formula weight: 77653.39

Authors

Andersen, C.B.,Wan, Y.,Chang, J.W.,Lee, C.,Liu, Y.,Sessa, F.,Villa, F.,Nallan, L.,Musacchio, A.,Gray, N.S. (deposition date: 2007-11-15, release date: 2008-02-26, Last modification date: 2024-11-13)

Primary citation

Andersen, C.B.,Wan, Y.,Chang, J.W.,Riggs, B.,Lee, C.,Liu, Y.,Sessa, F.,Villa, F.,Kwiatkowski, N.,Suzuki, M.,Nallan, L.,Heald, R.,Musacchio, A.,Gray, N.S.
Discovery of Selective Aminothiazole Aurora Kinase Inhibitors
Acs Chem.Biol., 3:180-, 2008

PubMed Abstract: Aurora family kinases regulate important events during mitosis including centrosome maturation and separation, mitotic spindle assembly, and chromosome segregation. Misregulation of Aurora kinases due to genetic amplification and protein overexpression results in aneuploidy and may contribute to tumorigenesis. Here we report the discovery of new small molecule aminothiazole inhibitors of Aurora kinases with exceptional kinase selectivity and report a 1.7 A cocrystal structure with the Aurora B:INCENP complex from Xenopus laevis. The compounds recapitulate the hallmarks of Aurora kinase inhibition, including decreased histone H3 serine 10 phosphorylation, failure to complete cytokinesis, and endoreduplication.

PubMed: 18307303
DOI: 10.1021/CB700200W

Experimental method

X-RAY DIFFRACTION (1.7 Å)