biostudies-literatureThirugnanasambantham PNIH HHS1102https://www.ebi.ac.uk/biostudies/studies/S-EPMC9609667biostudies-literatureUnknown11(10)Although salmonellosis, an infectious disease, is a significant global healthcare burden, there are no <i>Salmonella</i>-specific vaccines or therapeutics for humans. Motivated by our finding that FraB, a <i>Salmonella</i> deglycase responsible for fructose-asparagine catabolism, is a viable drug target, we initiated experimental and computational efforts to identify inhibitors of FraB. To this end, our recent high-throughput screening initiative yielded almost exclusively uncompetitive inhibitors of FraB. In parallel with this advance, we report here how a separate structural and computational biology investigation of FrlB, a FraB paralog, led to the serendipitous discovery that 2-deoxy-6-phosphogluconate is a competitive inhibitor of FraB (K_I ~ 3 μM). However, this compound waPathogens (Basel, Switzerland)Serendipitous Discovery of a Competitive Inhibitor of FraB, a <i>Salmonella</i> Deglycase and Drug Target.PMC9609667NIAID AI140541Behrman EJCapua ADWysocki VHLindert SAhmer BMMThirugnanasambantham PMitton-Fry MSabag-Daigle AGopalan VCool ABoulanger EFGao YKovvali SfalseSerendipitous Discovery of a Competitive Inhibitor of FraB, a <i>Salmonella</i> Deglycase and Drug Target.Although salmonellosis, an infectious disease, is a significant global healthcare burden, there are no <i>Salmonella</i>-specific vaccines or therapeutics for humans. Motivated by our finding that FraB, a <i>Salmonella</i> deglycase responsible for fructose-asparagine catabolism, is a viable drug target, we initiated experimental and computational efforts to identify inhibitors of FraB. To this end, our recent high-throughput screening initiative yielded almost exclusively uncompetitive inhibitors of FraB. In parallel with this advance, we report here how a separate structural and computational biology investigation of FrlB, a FraB paralog, led to the serendipitous discovery that 2-deoxy-6-phosphogluconate is a competitive inhibitor of FraB (K_I ~ 3 μM). However, this compound wa2022-01-01T00:00:00Z2022 Sep2025-04-18T21:21:38.772Z2024-12-03T15:39:06.022ZS-EPMC96096673629715910.3390/pathogens11101102