2CI7

Crystal structure of Dimethylarginine Dimethylaminohydrolase I in complex with Zinc, high pH

2CI7 の概要

• エントリーDOI: 10.2210/pdb2ci7/pdb
• 関連するPDBエントリー: 2C6Z 2CI1 2CI3 2CI4 2CI5 2CI6
• 分子名称: NG, NG-DIMETHYLARGININE DIMETHYLAMINOHYDROLASE 1, GLYCINE, ZINC ION, ... (4 entities in total)
• 機能のキーワード: nos regulation, s-nitrosylation, zinc, hydrolase, no, mma, adma, acetylation, metal-binding
• 由来する生物種: BOS TAURUS (BOVINE)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 31339.15

構造登録者

Frey, D.,Braun, O.,Briand, C.,Vasak, M.,Grutter, M.G. (登録日: 2006-03-17, 公開日: 2006-05-17, 最終更新日: 2023-12-13)

主引用文献

Frey, D.,Braun, O.,Briand, C.,Vasak, M.,Grutter, M.G.
Structure of the Mammalian Nos Regulator Dimethylarginine Dimethylaminohydrolase: A Basis for the Design of Specific Inhibitors.
Structure, 14:901-, 2006

PubMed Abstract: 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.

PubMed: 16698551
DOI: 10.1016/J.STR.2006.03.006

実験手法

X-RAY DIFFRACTION (1.6 Å)