Structure-Based Inhibitors Exhibit Differential Activities againstHelicobacter pyloriandEscherichia coliUndecaprenyl Pyrophosphate Synthases

[摘要] Helicobacter pyloricolonizes the human gastric epithelium and causes diseases such as gastritis, peptic ulcers, and stomach cancer. Undecaprenyl pyrophosphate synthase (UPPS), which catalyzes consecutive condensation reactions of farnesyl pyrophosphate with eight isopentenyl pyrophosphateto form lipid carrier for bacterial peptidoglycan biosynthesis, represents a potential target for developing new antibiotics. In this study, we solved the crystal structure ofH. pyloriUPPS and performed virtual screening of inhibitors from a library of 58,635 compounds. Two hits were found to exhibit differential activities againstHelicobacter pyloriandEscherichia coliUPPS, giving the possibility of developing antibiotics specially targeting pathogenicH. pyloriwithout killing the intestinalE. coli.

[学科分类] 基础医学