Inhibitors of the Bacterial Enzyme ArgE as Potential Novel Antibiotics

Bacteria are becoming increasingly resistant to antibiotics, and therefore there is an urgent need to discover novel antibiotics targeting alternate pathways. This project studies inhibitors of dizinc metalloenzyme acetylornithine deacetylase (ArgE), an enzyme found in the arginine biosynthesis pathway of bacteria. Inhibiting this enzyme would kill bacteria without mechanism-based toxicity to humans. We screened classes of potential inhibitors and tested compounds in a 214 nm assay, finding IC50 values for the most potent inhibitors. We also tested select inhibitors in a thermal shift assay with Escherichia coli ArgE to determine the stability of the enzyme in the presence of inhibitors.