Targeting Bacterial Nitric Oxide Synthase with Aminoquinoline-Based Inhibitors.
Biochemistry
; 55(39): 5587-5594, 2016 Oct 04.
Article
in En
| MEDLINE
| ID: mdl-27607918
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Staphylococcus aureus
/
Bacillus anthracis
/
Nitric Oxide Synthase
/
Enzyme Inhibitors
/
Aminoquinolines
Type of study:
Prognostic_studies
Language:
En
Journal:
Biochemistry
Year:
2016
Type:
Article
Affiliation country:
United States