A picomolar transition state analogue inhibitor of MTAN as a specific antibiotic for Helicobacter pylori.
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ABSTRACT:
SUBMITTER: Wang S
PROVIDER: S-EPMC3437630 | biostudies-literature | 2012 Sep
REPOSITORIES: biostudies-literature
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A picomolar transition state analogue inhibitor of MTAN as a specific antibiotic for Helicobacter pylori.
Wang Shanzhi S Haapalainen Antti M AM Yan Funing F Du Quan Q Tyler Peter C PC Evans Gary B GB Rinaldo-Matthis Agnes A Brown Rosemary L RL Norris Gillian E GE Almo Steven C SC Schramm Vern L VL
Biochemistry 20120822 35
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 MIC(90) 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- ...[more]
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