A picomolar transition state analogue inhibitor of MTAN as a specific antibiotic for helicobacter pylori

Shanzhi Wang, Antti M. Haapalainen, Funing Yan, Quan Du, Peter C. Tyler, Gary B. Evans, Agnes Rinaldo-Matthis, Rosemary L. Brown, Gillian E. Norris, Steven C. Almo, Vern L. Schramm

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Campylobacter and Helicobacter species express a 6-amino-6-deoxyfutalosine N-ribosylhydrolase (HpMTAN) proposed to function in menaquinone synthesis. BuT-DADMe-ImmA is a 36 pM transition state analogue of HpMTAN, and the crystal structure of the enzyme-inhibitor complex reveals the mechanism of inhibition. BuT-DADMe-ImmA has a MIC90 value of <8 ng/mL for Helicobacter pylori growth but does not cause growth arrest in other common clinical pathogens, thus demonstrating potential as an H. pylori-specific antibiotic.

Original languageEnglish (US)
Pages (from-to)6892-6894
Number of pages3
JournalBiochemistry
Volume51
Issue number35
DOIs
StatePublished - Sep 4 2012

ASJC Scopus subject areas

  • Biochemistry

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    Wang, S., Haapalainen, A. M., Yan, F., Du, Q., Tyler, P. C., Evans, G. B., Rinaldo-Matthis, A., Brown, R. L., Norris, G. E., Almo, S. C., & Schramm, V. L. (2012). A picomolar transition state analogue inhibitor of MTAN as a specific antibiotic for helicobacter pylori. Biochemistry, 51(35), 6892-6894. https://doi.org/10.1021/bi3009664