1h70

From Proteopedia

Revision as of 14:25, 5 November 2007

DDAH FROM PSEUDOMONAS AERUGINOSA. C249S MUTANT COMPLEXED WITH CITRULLINE

Overview

Nitric oxide synthase is inhibited by asymmetric NG-methylated derivatives, of arginine whose cellular levels are controlled in part by, dimethylarginine dimethylaminohydrolase (DDAH, EC 3.5.3.18). Levels of, asymmetric NG,NG-dimethylarginine (ADMA) are known to correlate with, certain disease states. Here, the first structure of a DDAH shows an, unexpected similarity to arginine:glycine amidinotransferase (EC 2.1.4.1), and arginine deiminase (EC 3.5.3.6), thus defining a superfamily of, arginine-modifying enzymes. The identification of a Cys-His-Glu catalytic, triad and the structures of a Cys to Ser point mutant bound to both, substrate and product suggest a reaction mechanism. Comparison of the, ADMA-DDAH and arginine-amidinotransferase complexes reveals a dramatic, rotation of the substrate that effectively maintains the orientation of, the scissile bond of the substrate with respect to the catalytic residues., The DDAH structure will form a basis for the rational design of selective, inhibitors, which are of potential use in modulating NO synthase activity, in pathological settings.

About this Structure

1H70 is a Single protein structure of sequence from Pseudomonas aeruginosa with CIR as ligand. Active as Dimethylargininase, with EC number 3.5.3.18 Structure known Active Site: CIR. Full crystallographic information is available from OCA.

Reference

Structural insights into the hydrolysis of cellular nitric oxide synthase inhibitors by dimethylarginine dimethylaminohydrolase., Murray-Rust J, Leiper J, McAlister M, Phelan J, Tilley S, Santa Maria J, Vallance P, McDonald N, Nat Struct Biol. 2001 Aug;8(8):679-83. PMID:11473257

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