1ED5

BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH NNA(H4B FREE)

1ED5 の概要

• エントリーDOI: 10.2210/pdb1ed5/pdb
• 関連するPDBエントリー: 1ED4 1ED6 8NSE
• 分子名称: NITRIC OXIDE SYNTHASE, ACETATE ION, PROTOPORPHYRIN IX CONTAINING FE, ... (8 entities in total)
• 機能のキーワード: nitric oxide synthase, heme protein, alpha-beta fold, oxidoreductase
• 由来する生物種: Bos taurus (cattle)
• 細胞内の位置: Cell membrane: P29473
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 101919.45

構造登録者

Raman, C.S.,Li, H.,Martasek, P.,Southan, G.J.,Masters, B.S.S.,Poulos, T.L. (登録日: 2000-01-26, 公開日: 2001-01-31, 最終更新日: 2023-11-15)

主引用文献

Raman, C.S.,Li, H.,Martasek, P.,Southan, G.,Masters, B.S.,Poulos, T.L.
Crystal structure of nitric oxide synthase bound to nitro indazole reveals a novel inactivation mechanism.
Biochemistry, 40:13448-13455, 2001

PubMed Abstract: Nitric oxide is generated under normal and pathophysiological conditions by three distinct isoforms of nitric oxide synthase (NOS). A small-molecule inhibitor of NOS (3-Br-7-nitroindazole, 7-NIBr) is profoundly neuroprotective in mouse models of stroke and Parkinson's disease. We report the crystal structure of the catalytic heme domain of endothelial NOS complexed with 7-NIBr at 1.65 A resolution. Critical to the binding of 7-NIBr at the substrate site is the adoption by eNOS of an altered conformation, in which a key glutamate residue swings out toward one of the heme propionate groups. Perturbation of the heme propionate ensues and eliminates the cofactor tetrahydrobiopterin-heme interaction. We also present three crystal structures that reveal how alterations at the substrate site facilitate 7-NIBr and structurally dissimilar ligands to occupy the cofactor site.

PubMed: 11695891
DOI: 10.1021/bi010957u

実験手法

X-RAY DIFFRACTION (1.8 Å)