title: Structure-based inhibitors exhibit differential activities against Helicobacter pylori and Escherichia coli undecaprenyl pyrophosphate synthases.
abstract: Helicobacter pylori colonizes 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 pyrophosphate to form lipid carrier for bacterial peptidoglycan biosynthesis, represents a potential target for developing new antibiotics. In this study, we solved the crystal structure of H. pylori UPPS and performed virtual screening of inhibitors from a library of 58,635 compounds. Two hits were found to exhibit differential activities against Helicobacter pylori and Escherichia coli UPPS, giving the possibility of developing antibiotics specially targeting pathogenic H. pylori without killing the intestinal E. coli.
authors.affiliation: Taiwan International Graduate Program, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Chih-Jung
authors.initials: CJ
authors.lastname: Kuo
authors.forename: Rey-Ting
authors.initials: RT
authors.lastname: Guo
authors.forename: I-Lin
authors.initials: IL
authors.lastname: Lu
authors.forename: Hun-Ge
authors.initials: HG
authors.lastname: Liu
authors.forename: Su-Ying
authors.initials: SY
authors.lastname: Wu
authors.forename: Tzu-Ping
authors.initials: TP
authors.lastname: Ko
authors.forename: Andrew H-J
authors.initials: AH
authors.lastname: Wang
authors.forename: Po-Huang
authors.initials: PH
authors.lastname: Liang
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors* / Q000648:ultrastructure*; D001665:Binding Sites; D003198:Computer Simulation; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000737:chemistry*; D004795:Enzyme Stability; D004926:Escherichia coli / Q000201:enzymology*; D016480:Helicobacter pylori / Q000201:enzymology*; D008956:Models, Chemical; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D004791:Enzyme Inhibitors; D019883:Alkyl and Aryl Transferases; C023266:undecaprenyl pyrophosphate synthetase