5G6P

Structure of Bacillus subtilis Nitric Oxide Synthase I218V in complex with 7-((4-(Dimethylamino)methyl)phenoxy)methyl)quinolin-2- amine

Summary for 5G6P

• Entry DOI: 10.2210/pdb5g6p/pdb
• Related: 5G65 5G66 5G67 5G68 5G69 5G6A 5G6B 5G6C 5G6D 5G6E 5G6F 5G6G 5G6H 5G6I 5G6J 5G6K 5G6L 5G6M 5G6N 5G6O 5G6Q
• Descriptor: NITRIC OXIDE SYNTHASE OXYGENASE, PROTOPORPHYRIN IX CONTAINING FE, CHLORIDE ION, ... (6 entities in total)
• Functional Keywords: nitric oxide synthase, oxidoreductase, inhibitor
• Biological source: BACILLUS SUBTILIS
• Total number of polymer chains: 1
• Total formula weight: 43131.87

Authors

Holden, J.K.,Poulos, T.L. (deposition date: 2016-06-18, release date: 2016-09-21, Last modification date: 2024-01-10)

Primary citation

Holden, J.K.,Lewis, M.C.,Cinelli, M.A.,Abdullatif, Z.,Pensa, A.V.,Silverman, R.B.,Poulos, T.L.
Targeting Bacterial Nitric Oxide Synthase with Aminoquinoline-Based Inhibitors.
Biochemistry, 55:5587-5594, 2016

PubMed 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.

PubMed: 27607918
DOI: 10.1021/acs.biochem.6b00786

Experimental method

X-RAY DIFFRACTION (2.18 Å)