title: Identification of small molecules that disrupt SSB-protein interactions using a high-throughput screen.
abstract: Bacterial single-stranded DNA-binding proteins (SSBs) recruit a diverse array of genome maintenance enzymes to their sites of action through direct protein interactions. The essential nature of these SSB-protein interactions makes inhibitors that block SSB-partner complex formation valuable biochemical tools and attractive potential antibacterial agents. However, many of these protein-protein interactions are weak and not amenable to the high-throughput nature of small molecule screens. Here I describe a high-throughput screen to identify small molecules that inhibit the interaction between Exonuclease I (ExoI) and the final 10 amino acids of the SSB C-terminal tail (SSB-Ct). The strength of the binding between ExoI and the SSB-Ct tail is fundamental to the interaction's utility in the high-throughput screen.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA, USA. bernstei@wi.mit.edu
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Bernstein
mesh_terms: D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005090:Exodeoxyribonucleases / Q000737:chemistry / Q000378:metabolism*; D057166:High-Throughput Screening Assays / Q000379:methods*; D008967:Molecular Biology / Q000379:methods; D011485:Protein Binding / Q000187:drug effects*
chemical_list: D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D005090:Exodeoxyribonucleases; C028450:exodeoxyribonuclease I