Pre-Steady-State Kinetic Characterization of an Antibiotic-Resistant Mutant of Staphylococcus aureus DNA Polymerase PolC.

ABSTRACT: The emergence and spread of antibiotic resistance in bacterial pathogens are serious and ongoing threats to public health. Since chromosome replication is essential to cell growth and pathogenesis, the essential DNA polymerases in bacteria have long been targets of antimicrobial development, although none have yet advanced to the market. Here, we use transient-state kinetic methods to characterize the inhibition of the PolC replicative DNA polymerase from Staphylococcus aureus by 2-methoxyethyl-6-(3'-ethyl-4'-methylanilino)uracil (ME-EMAU), a member of the 6-anilinouracil compounds that specifically target PolC enzymes, which are found in low-GC content Gram-positive bacteria. We find that ME-EMAU binds to S. aureus PolC with a dissociation constant of 14 nM, more than 200-fold tighter tha

SUBMITTER: Nelson-Rigg R 

PROVIDER: S-EPMC10269047 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature