title: Structural and biological studies on bacterial nitric oxide synthase inhibitors.
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.
authors.affiliation: Departments of Molecular Biology and Biochemistry, Pharmaceutical Sciences, and Chemistry, University of California, Irvine, CA 92697-3900.
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Holden
authors.forename: Huiying
authors.initials: H
authors.lastname: Li
authors.forename: Qing
authors.initials: Q
authors.lastname: Jing
authors.forename: Soosung
authors.initials: S
authors.lastname: Kang
authors.forename: Jerry
authors.initials: J
authors.lastname: Richo
authors.forename: Richard B
authors.initials: RB
authors.lastname: Silverman
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Poulos
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects* / Q000254:growth & development; D020134:Catalytic Domain / Q000235:genetics; D003001:Cloning, Molecular; D003460:Crystallization; D006418:Heme / Q000378:metabolism; D007093:Imidazoles / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D018384:Oxidative Stress / Q000502:physiology; D011485:Protein Binding; D051381:Rats; D012044:Regression Analysis
chemical_list: D000900:Anti-Bacterial Agents; D007093:Imidazoles; D006418:Heme; C029899:imidazole; D019001:Nitric Oxide Synthase
keywords: antibiotics; crystallography