P28: Inhibition of bacterial growth by the inhibitors of DnaQ-like exonucleases

The family of DnaQ-like exonucleases constitutes thousands of members, all with exonuclease activity that can process nucleic acids by removing one nucleotide at a time from 3′ to 5′ end. They all have the conserved DEDD domain with four acidic DEDD residues for binding of two magnesium ions in the active site. The DnaQ-like exonucleases bear various essential functions in prokaryotic or eukaryotic cells, including RNA maturation, RNA turnover, DNA replication and DNA repair. It has been shown that knockout of RNase T, one of the DnaQ-like exonucleases, generates a slow growth phenotype in E. coli, suggesting that inhibition of RNase T might be a way to reduce bacterial cell growth. Here we screen the compounds for the inhibition of the DnaQ-like exonucleases, including CRN-4, RNase T and TREX1, and found several potential inhibitors that can reduce the exonuclease activities of these enzymes. These compounds might be useful for the development of antibiotic or antivial agents.