2ci7

From Proteopedia

Revision as of 17:13, 18 December 2007

CRYSTAL STRUCTURE OF DIMETHYLARGININE DIMETHYLAMINOHYDROLASE I IN COMPLEX WITH ZINC, HIGH PH

Overview

Dimethylarginine dimethylaminohydrolase (DDAH) is involved in the, regulation of nitric oxide synthase (NOS) by metabolizing the free, endogenous arginine derivatives N(omega)-methyl-L-arginine (MMA) and, N(omega),N(omega)-dimethyl-L-arginine (ADMA), which are competitive, inhibitors of NOS. Here, we present high-resolution crystal structures of, DDAH isoform 1 (DDAH-1) isolated from bovine brain in complex with, different inhibitors, including S-nitroso-L-homocysteine and Zn2+, a, regulator of this mammalian enzyme. The structure of DDAH-1 consists of a, propeller-like fold similar to other arginine-modifying enzymes and a, flexible loop, which adopts different conformations and acts as a lid at, the entrance of the active site. The orientation and interaction mode of, inhibitors in the active site give insight into the regulation and the, molecular mechanism of the enzyme. The presented structures provide a, basis for the structure-based development of specific DDAH-1 inhibitors, that might be useful in the therapeutic treatment of NOS, dysfunction-related diseases.

About this Structure

2CI7 is a Single protein structure of sequence from Bos taurus with ZN and GLY as ligands. Active as Dimethylargininase, with EC number 3.5.3.18 Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

Structure of the mammalian NOS regulator dimethylarginine dimethylaminohydrolase: A basis for the design of specific inhibitors., Frey D, Braun O, Briand C, Vasak M, Grutter MG, Structure. 2006 May;14(5):901-11. PMID:16698551

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