1t4h

From Proteopedia

Revision as of 00:51, 21 November 2007

Crystal structure of the kinase domain of WNK1, a kinase that causes a hereditary form of hypertension

Overview

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.

About this Structure

1T4H is a Single protein structure of sequence from Rattus norvegicus. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.

Reference

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

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