4aw0 | pdb_00004aw0

Human PDK1 Kinase Domain in Complex with Allosteric Compound PS182 Bound to the PIF-Pocket

spinqualitylabelsall models 4aw0, resolution 1.43Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4aw0 is a 1 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: ATP, DMS, DTD, MG, MJF NonStd Res: CME, SEP Related: 1h1w, 1oky, 1okz, 1uu3, 1uu7, 1uu8, 1uu9, 1uvr, 1w1d, 1w1g, 1w1h, 1z5m, 2biy, 2vki, 2xch, 2xck, 4a06, 4a07, 4aw1 Activity: Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed The PIF-pocket of AGC protein kinases participates in the physiologic mechanism of regulation by acting as a docking site for substrates and as a switch for the transduction of the conformational changes needed for activation or inhibition. We describe the effects of compounds that bind to the PIF-pocket of PDK1. In vitro, PS210 is a potent activator of PDK1, and the crystal structure of the PDK1-ATP-PS210 complex shows that PS210 stimulates the closure of the kinase domain. However, in cells, the prodrug of PS210 (PS423) acts as a substrate-selective inhibitor of PDK1, inhibiting the phosphorylation and activation of S6K, which requires docking to the PIF-pocket, but not affecting PKB/Akt. This work describes a tool to study the dynamics of PDK1 activity and a potential approach for drug discovery. Substrate-Selective Inhibition of Protein Kinase PDK1 by Small Compounds that Bind to the PIF-Pocket Allosteric Docking Site.,Busschots K, Lopez-Garcia LA, Lammi C, Stroba A, Zeuzem S, Piiper A, Alzari PM, Neimanis S, Arencibia JM, Engel M, Schulze JO, Biondi RM Chem Biol. 2012 Sep 21;19(9):1152-63. doi: 10.1016/j.chembiol.2012.07.017. PMID:22999883 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also 3-phosphoinositide-dependent protein kinase 1

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