5G67

Structure of Bacillus subtilis Nitric Oxide Synthase in complex with 7-((3-Fluorophenethylamino)methyl)quinolin-2-amine

5G67 の概要

• エントリーDOI: 10.2210/pdb5g67/pdb
• 関連するPDBエントリー: 5G65 5G66 5G68 5G69 5G6A 5G6B 5G6C 5G6D 5G6E 5G6F 5G6G 5G6H 5G6I 5G6J 5G6K 5G6L 5G6M 5G6N 5G6O 5G6P 5G6Q
• 分子名称: NITRIC OXIDE SYNTHASE, PROTOPORPHYRIN IX CONTAINING FE, 5,6,7,8-TETRAHYDROBIOPTERIN, ... (9 entities in total)
• 機能のキーワード: nitric oxide synthase, oxidoreductase, inhibitor
• 由来する生物種: BACILLUS SUBTILIS
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 43326.03

構造登録者

Holden, J.K.,Poulos, T.L. (登録日: 2016-06-18, 公開日: 2016-09-21, 最終更新日: 2024-01-10)

主引用文献

Holden, J.K.,Lewis, M.C.,Cinelli, M.A.,Abdullatif, Z.,Pensa, A.V.,Silverman, R.B.,Poulos, T.L.
Targeting Bacterial Nitric Oxide Synthase with Aminoquinoline-Based Inhibitors.
Biochemistry, 55:5587-5594, 2016

PubMed Abstract: Nitric oxide is produced in Gram-positive pathogens Bacillus anthracis and Staphylococcus aureus by the bacterial isoform of nitric oxide synthase (NOS). Inhibition of bacterial nitric oxide synthase (bNOS) has been identified as a promising antibacterial strategy for targeting methicillin-resistant S. aureus [Holden, J. K., et al. (2015) Chem. Biol. 22, 785-779]. One class of NOS inhibitors that demonstrates antimicrobial efficacy utilizes an aminoquinoline scaffold. Here we report on a variety of aminoquinolines that target the bacterial NOS active site, in part, by binding to a hydrophobic patch that is unique to bNOS. Through mutagenesis and crystallographic studies, our findings demonstrate that aminoquinolines are an excellent scaffold for further aiding in the development of bNOS specific inhibitors.

PubMed: 27607918
DOI: 10.1021/acs.biochem.6b00786

実験手法

X-RAY DIFFRACTION (1.97 Å)