3hrf | pdb_00003hrf

Crystal structure of Human PDK1 kinase domain in complex with an allosteric activator bound to the PIF-pocket

spinqualitylabelsall models 3hrf, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3hrf is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ATP, EPE, P47 NonStd Res: SEP Related: 3hrc Gene: PDK1, PDPK1 (HUMAN) 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 Protein phosphorylation transduces a large set of intracellular signals. One mechanism by which phosphorylation mediates signal transduction is by prompting conformational changes in the target protein or interacting proteins. Previous work described an allosteric site mediating phosphorylation-dependent activation of AGC kinases. The AGC kinase PDK1 is activated by the docking of a phosphorylated motif from substrates. Here we present the crystallography of PDK1 bound to a rationally developed low-molecular-weight activator and describe the conformational changes induced by small compounds in the crystal and in solution using a fluorescence-based assay and deuterium exchange experiments. Our results indicate that the binding of the compound produces local changes at the target site, the PIF binding pocket, and also allosteric changes at the ATP binding site and the activation loop. Altogether, we present molecular details of the allosteric changes induced by small compounds that trigger the activation of PDK1 through mimicry of phosphorylation-dependent conformational changes. Structure and allosteric effects of low-molecular-weight activators on the protein kinase PDK1.,Hindie V, Stroba A, Zhang H, Lopez-Garcia LA, Idrissova L, Zeuzem S, Hirschberg D, Schaeffer F, Jorgensen TJ, Engel M, Alzari PM, Biondi RM Nat Chem Biol. 2009 Oct;5(10):758-64. Epub 2009 Aug 30. PMID:19718043 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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