3pyy

Discovery and Characterization of a Cell-Permeable, Small-molecule c-Abl Kinase Activator that Binds to the Myristoyl Binding Site

spinqualitylabelsall models 3pyy, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3pyy is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 2PE, 3YY, GOL, SO4, STI Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed c-Abl kinase activity is regulated by a unique mechanism involving the formation of an autoinhibited conformation in which the N-terminal myristoyl group binds intramolecularly to the myristoyl binding site on the kinase domain and induces the bending of the alphaI helix that creates a docking surface for the SH2 domain. Here, we report a small-molecule c-Abl activator, DPH, that displays potent enzymatic and cellular activity in stimulating c-Abl activation. Structural analyses indicate that DPH binds to the myristoyl binding site and prevents the formation of the bent conformation of the alphaI helix through steric hindrance, a mode of action distinct from the previously identified allosteric c-Abl inhibitor, GNF-2, that also binds to the myristoyl binding site. DPH represents the first cell-permeable, small-molecule tool compound for c-Abl activation. Discovery and Characterization of a Cell-Permeable, Small-Molecule c-Abl Kinase Activator that Binds to the Myristoyl Binding Site.,Yang J, Campobasso N, Biju MP, Fisher K, Pan XQ, Cottom J, Galbraith S, Ho T, Zhang H, Hong X, Ward P, Hofmann G, Siegfried B, Zappacosta F, Washio Y, Cao P, Qu J, Bertrand S, Wang DY, Head MS, Li H, Moores S, Lai Z, Johanson K, Burton G, Erickson-Miller C, Simpson G, Tummino P, Copeland RA, Oliff A Chem Biol. 2011 Feb 25;18(2):177-86. PMID:21338916 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Tyrosine kinase 3D structures

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