4JSJ

Structure of rat neuronal nitric oxide synthase heme domain in complex with 6-(((5-(((3-fluorophenethyl)amino)methyl)pyridin-3-yl)oxy)methyl)-4-methylpyridin-2-amine

4JSJ の概要

• エントリーDOI: 10.2210/pdb4jsj/pdb
• 関連するPDBエントリー: 4JSE 4JSF 4JSG 4JSH 4JSI 4JSK 4JSL 4JSM
• 分子名称: Nitric oxide synthase, brain, PROTOPORPHYRIN IX CONTAINING FE, 5,6,7,8-TETRAHYDROBIOPTERIN, ... (7 entities in total)
• 機能のキーワード: nitric oxide synthase, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• 由来する生物種: Rattus norvegicus (rat)
• 細胞内の位置: Cell membrane, sarcolemma ; Peripheral membrane protein : P29476
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 100256.88

構造登録者

Li, H.,Poulos, T.L. (登録日: 2013-03-22, 公開日: 2013-08-07, 最終更新日: 2023-09-20)

主引用文献

Jing, Q.,Li, H.,Fang, J.,Roman, L.J.,Martasek, P.,Poulos, T.L.,Silverman, R.B.
In search of potent and selective inhibitors of neuronal nitric oxide synthase with more simple structures.
Bioorg.Med.Chem., 21:5323-5331, 2013

PubMed Abstract: In certain neurodegenerative diseases damaging levels of nitric oxide (NO) are produced by neuronal nitric oxide synthase (nNOS). It, therefore, is important to develop inhibitors selective for nNOS that do not interfere with other NOS isoforms, especially endothelial NOS (eNOS), which is critical for proper functioning of the cardiovascular system. While we have been successful in developing potent and isoform-selective inhibitors, such as lead compounds 1 and 2, the ease of synthesis and bioavailability have been problematic. Here we describe a new series of compounds including crystal structures of NOS-inhibitor complexes that integrate the advantages of easy synthesis and good biological properties compared to the lead compounds. These results provide the basis for additional structure-activity relationship (SAR) studies to guide further improvement of isozyme selective inhibitors.

PubMed: 23867386
DOI: 10.1016/j.bmc.2013.06.014

実験手法

X-RAY DIFFRACTION (1.92 Å)