4PWN
Crystal structure of Active WNK1 kinase
Summary for 4PWN
| Entry DOI | 10.2210/pdb4pwn/pdb |
| Related | 3FPQ 4Q2A |
| Descriptor | Serine/threonine-protein kinase WNK1, PHOSPHATE ION (3 entities in total) |
| Functional Keywords | kinase, wnk1, ser/thr protein kinase, serine/threonine kinase, atp-binding, phosphorylation, transferase |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm : Q9H4A3 |
| Total number of polymer chains | 1 |
| Total formula weight | 31633.52 |
| Authors | Piala, A.,Moon, T.,Akella, T.,He, H.,Cobbm, M.H.,Goldsmith, E. (deposition date: 2014-03-20, release date: 2014-05-28, Last modification date: 2023-09-20) |
| Primary citation | Piala, A.T.,Moon, T.M.,Akella, R.,He, H.,Cobb, M.H.,Goldsmith, E.J. Chloride Sensing by WNK1 Involves Inhibition of Autophosphorylation. Sci.Signal., 7:ra41-ra41, 2014 Cited by PubMed Abstract: WNK1 [with no lysine (K)] is a serine-threonine kinase associated with a form of familial hypertension. WNK1 is at the top of a kinase cascade, leading to phosphorylation of several cotransporters, in particular those transporting sodium, potassium, and chloride (NKCC), sodium and chloride (NCC), and potassium and chloride (KCC). The responsiveness of NKCC, NCC, and KCC to changes in extracellular chloride parallels their phosphorylation state, provoking the proposal that these transporters are controlled by a chloride-sensitive protein kinase. We found that chloride stabilizes the inactive conformation of WNK1, preventing kinase autophosphorylation and activation. Crystallographic studies of inactive WNK1 in the presence of chloride revealed that chloride binds directly to the catalytic site, providing a basis for the unique position of the catalytic lysine. Mutagenesis of the chloride-binding site rendered the kinase less sensitive to inhibition of autophosphorylation by chloride, validating the binding site. Thus, these data suggest that WNK1 functions as a chloride sensor through direct binding of a regulatory chloride ion to the active site, which inhibits autophosphorylation. PubMed: 24803536DOI: 10.1126/scisignal.2005050 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.84 Å) |
Structure validation
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