Structural and biological studies on bacterial nitric oxide synthase inhibitors

被引：39

作者：

Holden, Jeffrey K. ^{[1
,2
,3
]}

Li, Huiying ^{[1
,2
,3
]}

Jing, Qing ^{[4
,5
]}

Kang, Soosung ^{[4
,5
]}

Richo, Jerry ^{[1
,2
,3
]}

Silverman, Richard B. ^{[4
,5
]}

Poulos, Thomas L. ^{[4
,5
]}

机构：

[1] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA

[2] Univ Calif Irvine, Dept Pharmaceut Sci, Irvine, CA 92697 USA

[3] Univ Calif Irvine, Dept Chem, Irvine, CA 92697 USA

[4] Northwestern Univ, Ctr Mol Innovat & Drug Discovery, Chem Life Proc Inst, Dept Chem, Evanston, IL 60208 USA

[5] Northwestern Univ, Ctr Mol Innovat & Drug Discovery, Chem Life Proc Inst, Dept Mol Biosci, Evanston, IL 60208 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2013年 / 110卷 / 45期

基金：

美国国家卫生研究院;

关键词：

crystallography; antibiotics; RATIONAL PROTEIN CRYSTALLIZATION; BACILLUS-SUBTILIS; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; ANTIBIOTICS; NITRATION; MECHANISM; MODE;

D O I：

10.1073/pnas.1314080110

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Nitric oxide (NO) produced by bacterial NOS functions as a cytoprotective agent against oxidative stress in Staphylococcus aureus, Bacillus anthracis, and Bacillus subtilis. The screening of several NOS- selective inhibitors uncovered two inhibitors with potential antimicrobial properties. These two compounds impede the growth of B. subtilis under oxidative stress, and crystal structures show that each compound exhibits a unique binding mode. Both compounds serve as excellent leads for the future development of antimicrobials against bacterial NOS- containing bacteria.

引用

页码：18127 / 18131

页数：5

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