A Picomolar Transition State Analogue Inhibitor of MTAN as a Specific Antibiotic for Helicobacter pylori

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• 作者：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
• 刊名：Biochemistry
• 出版年：2012
• 出版时间：September 4, 2012
• 年：2012
• 卷：51
• 期：35
• 页码：6892-6894
• 全文大小：212K
• 年卷期：v.51,no.35(September 4, 2012)
• ISSN：1520-4995

文摘

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鈥搃nhibitor 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.