A Picomolar Transition State Analogue Inhibitor of MTAN as a Specific Antibiotic for Helicobacter pylori
2012
Wang, Shanzhi | Haapalainen, Antti M. | Yan, Funing | Du, Quan | Tyler, Peter C. | Evans, Gary B. | Rinaldo-Matthis, Agnes | Brown, Rosemary L. | Norris, Gillian E. | Almo, Steven C. | Schramm, Vern L.
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.
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