Structure-Based Discovery of Small Molecule Inhibitors of Cariogenic Virulence.

ABSTRACT: Streptococcus mutans employs a key virulence factor, three glucosyltransferase (GtfBCD) enzymes to establish cariogenic biofilms. Therefore, the inhibition of GtfBCD would provide anti-virulence therapeutics. Here a small molecule library of 500,000 small molecule compounds was screened in silico against the available crystal structure of the GtfC catalytic domain. Based on the predicted binding affinities and drug-like properties, small molecules were selected and evaluated for their ability to reduce S. mutans biofilms, as well as inhibit the activity of Gtfs. The most potent inhibitor was further characterized for Gtf binding using OctetRed instrument, which yielded low micromolar K_D against GtfB and nanomolar K_D against GtfC, demonstrating selectivity towards GtfC

SUBMITTER: Zhang Q 

PROVIDER: S-EPMC5519559 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature