Fragment-Based Discovery of Inhibitors of the Bacterial DnaG-SSB Interaction.

ABSTRACT: In bacteria, the DnaG primase is responsible for synthesis of short RNA primers used to initiate chain extension by replicative DNA polymerase(s) during chromosomal replication. Among the proteins with which Escherichia coli DnaG interacts is the single-stranded DNA-binding protein, SSB. The C-terminal hexapeptide motif of SSB (DDDIPF; SSB-Ct) is highly conserved and is known to engage in essential interactions with many proteins in nucleic acid metabolism, including primase. Here, fragment-based screening by saturation-transfer difference nuclear magnetic resonance (STD-NMR) and surface plasmon resonance assays identified inhibitors of the primase/SSB-Ct interaction. Hits were shown to bind to the SSB-Ct-binding site using ¹⁵N-¹H HSQC spectra. STD-NMR was used to demonst

SUBMITTER: Chilingaryan Z 

PROVIDER: S-EPMC5872125 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature