3RQL

Structure of the neuronal nitric oxide synthase heme domain in complex with 6-(((3R,4R)-4-(2-((1S,2R/1R,2S)-2-(3-Clorophenyl)cyclopropylamino)ethoxy)pyrrolidin-3-yl)methyl)-4-methylpyridin-2-amine

3RQL の概要

• エントリーDOI: 10.2210/pdb3rql/pdb
• 関連するPDBエントリー: 3RQJ 3RQK 3RQM 3RQN 3RQO 3RQP
• 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: oxidoreductase, enzyme-inhibitor complex, oxidoreductase-inhibitor complex, oxidoreductase/inhibitor
• 由来する生物種: Rattus norvegicus (brown rat,rat,rats)
• 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: 100325.91

構造登録者

Li, H.,Delker, S.L.,Poulos, T.L. (登録日: 2011-04-28, 公開日: 2012-05-02, 最終更新日: 2023-09-13)

主引用文献

Li, H.,Xue, F.,Kraus, J.M.,Ji, H.,Labby, K.J.,Mataka, J.,Delker, S.L.,Martasek, P.,Roman, L.J.,Poulos, T.L.,Silverman, R.B.
Cyclopropyl- and methyl-containing inhibitors of neuronal nitric oxide synthase.
Bioorg.Med.Chem., 21:1333-1343, 2013

PubMed Abstract: Inhibitors of neuronal nitric oxide synthase have been proposed as therapeutics for the treatment of different types of neurological disorders. On the basis of a cis-3,4-pyrrolidine scaffold, a series of trans-cyclopropyl- and methyl-containing nNOS inhibitors have been synthesized. The insertion of a rigid electron-withdrawing cyclopropyl ring decreases the basicity of the adjacent amino group, which resulted in decreased inhibitory activity of these inhibitors compared to the parent compound. Nonetheless, three of them exhibited double-digit nanomolar inhibition with high nNOS selectivity on the basis of in vitro enzyme assays. Crystal structures of nNOS and eNOS with these inhibitors bound provide a basis for detailed structure-activity relationship (SAR) studies. The conclusions from these studies will be used as a guide in the future development of selective NOS inhibitors.

PubMed: 23352768
DOI: 10.1016/j.bmc.2012.12.019

実験手法

X-RAY DIFFRACTION (1.93 Å)