3TYM

Structure of neuronal nitric oxide synthase heme domain in complex with 6-(((3S,4S)-4-(2-((2-methoxybenzyl)amino)ethoxy)pyrrolidin-3-yl)methyl)-4-methylpyridin-2-amine

3TYM の概要

• エントリーDOI: 10.2210/pdb3tym/pdb
• 関連するPDBエントリー: 3TYL 3TYN 3TYO
• 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, inhibitor binding, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/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: 100265.00

構造登録者

Li, H.,Poulos, T.L. (登録日: 2011-09-26, 公開日: 2012-03-14, 最終更新日: 2023-09-13)

主引用文献

Labby, K.J.,Xue, F.,Kraus, J.M.,Ji, H.,Mataka, J.,Li, H.,Martasek, P.,Roman, L.J.,Poulos, T.L.,Silverman, R.B.
Intramolecular hydrogen bonding: A potential strategy for more bioavailable inhibitors of neuronal nitric oxide synthase.
Bioorg.Med.Chem., 20:2435-2443, 2012

PubMed Abstract: Selective neuronal nitric oxide synthase (nNOS) inhibitors have therapeutic applications in the treatment of numerous neurodegenerative diseases. Here we report the synthesis and evaluation of a series of inhibitors designed to have increased cell membrane permeability via intramolecular hydrogen bonding. Their potencies were examined in both purified enzyme and cell-based assays; a comparison of these results demonstrates that two of the new inhibitors display significantly increased membrane permeability over previous analogs. NMR spectroscopy provides evidence of intramolecular hydrogen bonding under physiological conditions in two of the inhibitors. Crystal structures of the inhibitors in the nNOS active site confirm the predicted non-intramolecular hydrogen bonded binding mode. Intramolecular hydrogen bonding may be an effective approach for increasing cell membrane permeability without affecting target protein binding.

PubMed: 22370337
DOI: 10.1016/j.bmc.2012.01.037

実験手法

X-RAY DIFFRACTION (2 Å)