1D1V

BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH S-ETHYL-N-PHENYL-ISOTHIOUREA (H4B BOUND)

1D1V の概要

• エントリーDOI: 10.2210/pdb1d1v/pdb
• 関連するPDBエントリー: 1D0C 1D0O 1D1V 1D1W 1D1X 1D1Y 1NSE
• 分子名称: BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME, ACETATE ION, ZINC ION, ... (9 entities in total)
• 機能のキーワード: 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: 102257.99

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: 1999-09-21, 公開日: 2001-07-25, 最終更新日: 2024-02-07)

主引用文献

Raman, C.S.,Li, H.,Martasek, P.,Babu, B.R.,Griffith, O.W.,Masters, B.S.,Poulos, T.L.
Implications for isoform-selective inhibitor design derived from the binding mode of bulky isothioureas to the heme domain of endothelial nitric-oxide synthase.
J.Biol.Chem., 276:26486-26491, 2001

PubMed Abstract: Nitric oxide produced by nitric-oxide synthase (NOS) is not only involved in a wide range of physiological functions but also in a variety of pathological conditions. Isoform-selective NOS inhibitors are highly desirable to regulate the NO production of one isoform beneficial to normal physiological functions from the uncontrolled NO production of another isoform that accompanies certain pathological states. Crystal structures of the heme domain of the three NOS isoforms have revealed a very high degree of similarity in the immediate vicinity of the heme active site illustrating the challenge of isoform-selective inhibitor design. Isothioureas are potent NOS inhibitors, and the structures of the endothelial NOS heme domain complexed with isothioureas bearing small S-alkyl substituents have been determined (Li, H., Raman, C.S., Martásek, P., Král, V., Masters, B.S.S., and Poulos, T.L. (2000) J. Inorg. Biochem. 81, 133--139). In the present communication, the binding mode of larger bisisothioureas complexed to the endothelial NOS heme domain has been determined. These structures afford a structural rationale for the known inhibitory activities. In addition, these structures provide clues on how to exploit the longer inhibitor substituents that extend out of the active site pocket for isoform-selective inhibitor design.

PubMed: 11331290
DOI: 10.1074/jbc.M102255200

実験手法

X-RAY DIFFRACTION (1.93 Å)