6cn9 | pdb_00006cn9

Crystal structure of the Kinase domain of WNK1

spinqualitylabelsall models 6cn9, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6cn9 is a 2 chain structure with sequence from Buffalo rat. This structure supersedes the now removed PDB entries 3fpq and 1t4h. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL, SO4 NonStd Res: MSE Related: 3fpq Gene: Wnk1, Hsn2, Prkwnk1 (Buffalo rat) Activity: Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [WNK1_RAT] Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively. Activates SCNN1A, SCNN1B, SCNN1D and SGK1. Controls sodium and chloride ion transport by inhibiting the activity of WNK4, by either phosphorylating the kinase or via an interaction between WNK4 and the autoinhibitory domain of WNK1. WNK4 regulates the activity of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation. WNK1 may also play a role in actin cytoskeletal reorganization. Phosphorylates NEDD4L. Publication Abstract from PubMed WNK kinases comprise a small group of unique serine/threonine protein kinases that have been genetically linked to pseudohypoaldosteronism type II, an autosomal dominant form of hypertension. Here we present the structure of the kinase domain of WNK1 at 1.8 A resolution, solved in a low activity conformation. A lysine residue (Lys-233) is found in the active site emanating from strand beta2 rather than strand beta3 as in other protein kinases. The activation loop adopts a unique well-folded inactive conformation. The conformations of the P+1 specificity pocket, the placement of the conserved active site threonine (Thr-386), and the exterior placement of helix C, contribute to the low activity state. By homology modeling, we identified two hydrophobic residues in the substrate-binding groove that contribute to substrate specificity. The structure of the WNK1 catalytic domain, with its unique active site, may help in the design of therapeutic reagents for the treatment of hypertension. Crystal structure of the kinase domain of WNK1, a kinase that causes a hereditary form of hypertension.,Min X, Lee BH, Cobb MH, Goldsmith EJ Structure. 2004 Jul;12(7):1303-11. PMID:15242606 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Serine/threonine protein kinase 3D structures

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