Structure-based inhibitors exhibit differential activities against Helicobacter pylori and Escherichia coli undecaprenyl pyrophosphate synthases
Resource
Journal of Biomedicine and Biotechnology 2008: 841312
Journal
Journal of Biomedicine and Biotechnology
Pages
1
Date Issued
2008
Date
2008
Author(s)
Kuo, Chih-Jung
Guo, Rey-Ting
Lu, I-Lin
Liu, Hun-Ge
Wu, Su-Ying
Ko, Tzu-Ping
Wang, Andrew H.-J.
Liang, Po-Huang
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. Copyright ? 2008 Chih-Jung Kuo et al.
SDGs
Other Subjects
enzyme inhibitor; farnesyl diphosphate; isopentenyl diphosphate; peptidoglycan; synthetase; undecaprenyl pyrophosphate synthase; undecaprenyl pyrophosphate synthase inhibitor; decaprenyltransferase; enzyme inhibitor; transferase; article; biosynthesis; catalyst; computer model; crystal structure; data base; drug mechanism; drug specificity; drug targeting; enzyme active site; enzyme inhibition; enzyme structure; Escherichia coli; Helicobacter pylori; nonhuman; polymerization; structure analysis; binding site; chemical model; chemical structure; chemistry; comparative study; computer simulation; drug antagonism; enzyme activation; enzyme stability; enzymology; protein binding; protein conformation; ultrastructure; Bacteria (microorganisms); Escherichia coli; Helicobacter pylori; Alkyl and Aryl Transferases; Binding Sites; Computer Simulation; Enzyme Activation; Enzyme Inhibitors; Enzyme Stability; Escherichia coli; Helicobacter pylori; Models, Chemical; Models, Molecular; Protein Binding; Protein Conformation
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