Table of Contents Author Guidelines Submit a Manuscript
Journal of Biomedicine and Biotechnology
Volume 2008, Article ID 841312, 6 pages
http://dx.doi.org/10.1155/2008/841312
Research Article

Structure-Based Inhibitors Exhibit Differential Activities against Helicobacter pylori and Escherichia coli Undecaprenyl Pyrophosphate Synthases

1Taiwan International Graduate Program, Academia Sinica, Taipei 115, Taiwan
2Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan
3Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Chu-Nan, Miaw-Li 350, Taiwan
4Institute of Biological Chemistry, Academia Sinica, Taipei 11529, Taiwan

Received 21 September 2007; Accepted 27 December 2007

Academic Editor: Daniel Howard

Copyright © 2008 Chih-Jung Kuo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.