A Picomolar Transition State Analogue Inhibitor of MTAN As a Specific Antibiotic for Helicobacter Pylori

Overview

Journal Biochemistry

Specialty Biochemistry

Date 2012 Aug 16

PMID 22891633

Citations 31

Authors

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

Affiliations

Soon will be listed here.

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 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-specific antibiotic.

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