3cy2

Crystal structure of human proto-oncogene serine threonine kinase (PIM1) in complex with a consensus peptide and a beta carboline ligand IICrystal structure of human proto-oncogene serine threonine kinase (PIM1) in complex with a consensus peptide and a beta carboline ligand II

Structural highlights 3cy2 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , , Related: 3cxw, 3cy3 Gene: PIM1 (Homo sapiens) 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 Development of both potent and selective kinase inhibitors is a challenging task in modern drug discovery. The innate promiscuity of kinase inhibitors largely results from ATP-mimetic binding to the kinase hinge region. We present a novel class of substituted 7,8-dichloro-1-oxo-beta-carbolines based on the distinct structural features of the alkaloid bauerine C whose kinase inhibitory activity does not rely on canonical ATP-mimetic hinge interactions. Intriguingly, cocrystal structures revealed an unexpected inverted binding mode and the presence of halogen bonds with kinase backbone residues. The compounds exhibit excellent selectivity over a comprehensive panel of human protein kinases while inhibiting selected kinases such as the oncogenic PIM1 at low nanomolar concentrations. Together, our biochemical and structural data suggest that this scaffold may serve as a valuable template for the design and development of specific inhibitors of various kinases including the PIM family of kinases, CLKs, DAPK3 (ZIPK), BMP2K (BIKE), and others. 7,8-Dichloro-1-oxo-beta-carbolines as a Versatile Scaffold for the Development of Potent and Selective Kinase Inhibitors with Unusual Binding Modes.,Huber K, Brault L, Fedorov O, Gasser C, Filippakopoulos P, Bullock AN, Fabbro D, Trappe J, Schwaller J, Knapp S, Bracher F J Med Chem. 2012 Jan 12;55(1):403-13. Epub 2012 Jan 3. PMID:22136433 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Proto-oncogene serine/threonine-protein kinase

spinqualitylabelsall models 3cy2, resolution 2.01Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image