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

doi:10.1021/bi3009664

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 journal › Article › peer-review

47 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 language	English (US)
Pages (from-to)	6892-6894
Number of pages	3
Journal	Biochemistry
Volume	51
Issue number	35
DOIs	https://doi.org/10.1021/bi3009664
State	Published - Sep 4 2012

ASJC Scopus subject areas

Biochemistry

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title = "A picomolar transition state analogue inhibitor of MTAN as a specific antibiotic for helicobacter pylori",

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.",

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

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doi = "10.1021/bi3009664",

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T1 - A picomolar transition state analogue inhibitor of MTAN as a specific antibiotic for helicobacter pylori

AU - Wang, Shanzhi

AU - Haapalainen, Antti M.

AU - Yan, Funing

AU - Du, Quan

AU - Tyler, Peter C.

AU - Evans, Gary B.

AU - Rinaldo-Matthis, Agnes

AU - Brown, Rosemary L.

AU - Norris, Gillian E.

AU - Almo, Steven C.

AU - Schramm, Vern L.

PY - 2012/9/4

Y1 - 2012/9/4

N2 - 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.

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

Abstract

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