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 journalArticle

30 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)6892-6894
Number of pages3
JournalBiochemistry
Volume51
Issue number35
DOIs
StatePublished - Sep 4 2012

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Helicobacter pylori
Anti-Bacterial Agents
Helicobacter
Vitamin K 2
Campylobacter
Enzyme Inhibitors
Pathogens
Growth
Crystal structure
4'-deaza-1'-aza-2'-deoxy-1'-(9-methylene)-immucillin A

ASJC Scopus subject areas

  • Biochemistry

Cite this

A picomolar transition state analogue inhibitor of MTAN as a specific antibiotic for helicobacter pylori. / 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.

In: Biochemistry, Vol. 51, No. 35, 04.09.2012, p. 6892-6894.

Research output: Contribution to journalArticle

Wang, S, Haapalainen, AM, Yan, F, Du, Q, Tyler, PC, Evans, GB, Rinaldo-Matthis, A, Brown, RL, Norris, GE, Almo, SC & Schramm, VL 2012, 'A picomolar transition state analogue inhibitor of MTAN as a specific antibiotic for helicobacter pylori', Biochemistry, vol. 51, no. 35, pp. 6892-6894. https://doi.org/10.1021/bi3009664
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. / A picomolar transition state analogue inhibitor of MTAN as a specific antibiotic for helicobacter pylori. In: Biochemistry. 2012 ; Vol. 51, No. 35. pp. 6892-6894.
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