2yza

Crystal structure of kinase domain of Human 5'-AMP-activated protein kinase alpha-2 subunit mutant (T172D)

spinqualitylabelsall models 2yza, resolution 3.02Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2yza 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. Related: 2h6d Gene: PRKAA2, AMPK, AMPK2 (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 AMP-activated protein kinase (AMPK) is a serine/threonine kinase that functions as a sensor to maintain energy balance at both the cellular and the whole-body levels and is therefore a potential target for drug design against metabolic syndrome, obesity and type 2 diabetes. Here, the crystal structure of the phosphorylated-state mimic T172D mutant kinase domain from the human AMPK alpha2 subunit is reported in the apo form and in complex with a selective inhibitor, compound C. The AMPK alpha2 kinase domain exhibits a typical bilobal kinase fold and exists as a monomer in the crystal. Like the wild-type apo form, the T172D mutant apo form adopts the autoinhibited structure of the `DFG-out' conformation, with the Phe residue of the DFG motif anchored within the putative ATP-binding pocket. Compound C binding dramatically alters the conformation of the activation loop, which adopts an intermediate conformation between DFG-out and DFG-in. This induced fit forms a compound-C binding pocket composed of the N-lobe, the C-lobe and the hinge of the kinase domain. The pocket partially overlaps with the putative ATP-binding pocket. These three-dimensional structures will be useful to guide drug discovery. Structural basis for compound C inhibition of the human AMP-activated protein kinase alpha2 subunit kinase domain.,Handa N, Takagi T, Saijo S, Kishishita S, Takaya D, Toyama M, Terada T, Shirouzu M, Suzuki A, Lee S, Yamauchi T, Okada-Iwabu M, Iwabu M, Kadowaki T, Minokoshi Y, Yokoyama S Acta Crystallogr D Biol Crystallogr. 2011 May;67(Pt 5):480-7. Epub 2011 Apr 14. PMID:21543851 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also AMP-activated protein kinase

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