Serendipitous Discovery of a Competitive Inhibitor of FraB, a Salmonella Deglycase and Drug Target.

ABSTRACT: Although salmonellosis, an infectious disease, is a significant global healthcare burden, there are no Salmonella-specific vaccines or therapeutics for humans. Motivated by our finding that FraB, a Salmonella 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 wa

SUBMITTER: Thirugnanasambantham P 

PROVIDER: S-EPMC9609667 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature