4D7I

Structure of Bacillus subtilis nitric oxide synthase I218V in complex with 6-(4-(((3-Fluorophenethyl)amino)methyl)phenyl)-4-methylpyridin-2- amine

4D7I の概要

• エントリーDOI: 10.2210/pdb4d7i/pdb
• 関連するPDBエントリー: 4D7H 4D7J
• 分子名称: NITRIC OXIDE SYNTHASE OXYGENASE, PROTOPORPHYRIN IX CONTAINING FE, 5,6,7,8-TETRAHYDROBIOPTERIN, ... (7 entities in total)
• 機能のキーワード: oxidoreductase, nitric oxide synthase
• 由来する生物種: BACILLUS SUBTILIS SUBSP. SUBTILIS STR. 168
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 43093.75

構造登録者

Holden, J.K.,Poulos, T.L. (登録日: 2014-11-25, 公開日: 2015-07-01, 最終更新日: 2023-12-20)

主引用文献

Holden, J.K.,Kang, S.,Beasley, F.C.,Cinelli, M.A.,Li, H.,Roy, S.G.,Dejam, D.,Edinger, A.L.,Nizet, V.,Silverman, R.B.,Poulos, T.L.
Nitric Oxide Synthase as a Target for Methicillin-Resistant Staphylococcus Aureus
Chem.Biol., 22:785-, 2015

PubMed Abstract: Bacterial infections associated with methicillin-resistant Staphylococcus aureus (MRSA) are a major economic burden to hospitals, and confer high rates of morbidity and mortality among those infected. Exploitation of novel therapeutic targets is thus necessary to combat this dangerous pathogen. Here, we report on the identification and characterization, including crystal structures, of two nitric oxide synthase (NOS) inhibitors that function as antimicrobials against MRSA. These data provide the first evidence that bacterial NOS (bNOS) inhibitors can work synergistically with oxidative stress to enhance MRSA killing. Crystal structures show that each inhibitor contacts an active site Ile residue in bNOS that is Val in the mammalian NOS isoforms. Mutagenesis studies show that the additional nonpolar contacts provided by the Ile in bNOS contribute to tighter binding toward the bacterial enzyme.

PubMed: 26091171
DOI: 10.1016/J.CHEMBIOL.2015.05.013

実験手法

X-RAY DIFFRACTION (1.96 Å)