1H70

DDAH FROM PSEUDOMONAS AERUGINOSA. C249S MUTANT COMPLEXED WITH CITRULLINE

1H70 の概要

• エントリーDOI: 10.2210/pdb1h70/pdb
• 分子名称: NG, NG-DIMETHYLARGININE DIMETHYLAMINOHYDROLASE, CITRULLINE (3 entities in total)
• 機能のキーワード: hydrolase, ddah, nitric oxide synthase inhibitor
• 由来する生物種: PSEUDOMONAS AERUGINOSA
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 28812.82

構造登録者

Murray-Rust, J.,Leiper, J.,McAlister, M.,Phelan, J.,Tilley, S.,Santamaria, J.,Vallance, P.,McDonald, N. (登録日: 2001-06-30, 公開日: 2001-08-02, 最終更新日: 2024-05-01)

主引用文献

Murray-Rust, J.,Leiper, J.,McAlister, M.,Phelan, J.,Tilley, S.,Santa Maria, J.,Vallance, P.,McDonald, N.
Structural insights into the hydrolysis of cellular nitric oxide synthase inhibitors by dimethylarginine dimethylaminohydrolase.
Nat. Struct. Biol., 8:679-683, 2001

PubMed Abstract: 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.

PubMed: 11473257
DOI: 10.1038/90387

実験手法

X-RAY DIFFRACTION (1.8 Å)