1. High-Throughput Screening to Identify Inhibitors of SSB-Protein Interactions.
- Author
-
Voter AF
- Subjects
- Binding Sites, DNA Helicases chemistry, DNA-Binding Proteins chemistry, Drug Evaluation, Preclinical, High-Throughput Screening Assays, Models, Molecular, Protein Binding drug effects, Protein Conformation, DNA Helicases metabolism, DNA-Binding Proteins metabolism, Klebsiella pneumoniae metabolism, Small Molecule Libraries pharmacology
- Abstract
The bacterial single-stranded DNA-binding protein (SSB) uses an acidic C-terminal tail to interact with over a dozen proteins, acting as a genome maintenance hub. These SSB-protein interactions are essential, as mutations to the C-terminal tail that disrupt these interactions are lethal in Escherichia coli. While the roles of individual SSB-protein interactions have been dissected with mutational studies, small-molecule inhibitors of these interactions could serve as valuable research tools and have potential as novel antimicrobial agents. This chapter describes a high-throughput screening campaign used to identify inhibitors of SSB-protein interactions. A screen targeting the PriA-SSB interface from Klebsiella pneumoniae is presented as an example, but the methods may be adapted to target nearly any SSB interaction.
- Published
- 2021
- Full Text
- View/download PDF