Structural and biological studies on bacterial nitric oxide synthase inhibitors

Jeffrey K. Holden; Huiying Li; Qing Jing; Soosung Kang; Jerry Richo; Richard B. Silverman; Thomas L. Poulos

doi:10.1073/pnas.1314080110

Structural and biological studies on bacterial nitric oxide synthase inhibitors

Jeffrey K. Holden, Huiying Li, Qing Jing, Soosung Kang, Jerry Richo, Richard B. Silverman^*, Thomas L. Poulos

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

43 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	18127-18131
Number of pages	5
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	110
Issue number	45
DOIs	https://doi.org/10.1073/pnas.1314080110
State	Published - Nov 5 2013

Keywords

Antibiotics
Crystallography

ASJC Scopus subject areas

General

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10.1073/pnas.1314080110

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AU - Holden, Jeffrey K.

AU - Li, Huiying

AU - Jing, Qing

AU - Kang, Soosung

AU - Richo, Jerry

AU - Silverman, Richard B.

AU - Poulos, Thomas L.

PY - 2013/11/5

Y1 - 2013/11/5

N2 - 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.

AB - 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.

KW - Antibiotics

KW - Crystallography

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Structural and biological studies on bacterial nitric oxide synthase inhibitors

Abstract

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Structure of rat neuronal nitric oxide synthase heme domain in complex with 6-((((3R,5S)-5-(((6-amino-4-methylpyridin-2-yl)methoxy)methyl)pyrrolidin-3-yl)oxy)methyl)-4-methylpyridin-2-amine

Structure of Bacillus subtilis nitric oxide synthase in complex with ((2S, 3S)-1,3-bis((6-(2,5-dimethyl-1H-pyrrol-1-yl)-4-methylpyridin-2-yl)methoxy)-2-aminobutane

Structure of bovine endothelial nitric oxide synthase heme domain in complex with 6-((((3R,5S)-5-(((6-amino-4-methylpyridin-2-yl)methoxy)methyl)pyrrolidin-3-yl)oxy)methyl)-4-methylpyridin-2-amine

Cite this

Structural and biological studies on bacterial nitric oxide synthase inhibitors

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Datasets

Structure of rat neuronal nitric oxide synthase heme domain in complex with 6-((((3R,5S)-5-(((6-amino-4-methylpyridin-2-yl)methoxy)methyl)pyrrolidin-3-yl)oxy)methyl)-4-methylpyridin-2-amine

Structure of Bacillus subtilis nitric oxide synthase in complex with ((2S, 3S)-1,3-bis((6-(2,5-dimethyl-1H-pyrrol-1-yl)-4-methylpyridin-2-yl)methoxy)-2-aminobutane

Structure of bovine endothelial nitric oxide synthase heme domain in complex with 6-((((3R,5S)-5-(((6-amino-4-methylpyridin-2-yl)methoxy)methyl)pyrrolidin-3-yl)oxy)methyl)-4-methylpyridin-2-amine

Cite this