Antibacterial Strategy against H. pylori: Inhibition of the Radical SAM Enzyme MqnE in Menaquinone Biosynthesis

Sumedh Joshi, Dmytro Fedoseyenko, Nilkamal Mahanta, Rodrigo G. Ducati, Mu Feng, Vern L. Schramm, Tadhg P. Begley

Research output: Contribution to journalArticle

Abstract

Aminofutalosine synthase (MqnE) catalyzes an important rearrangement reaction in menaquinone biosynthesis by the futalosine pathway. In this Letter, we report the identification of previously unreported inhibitors of MqnE using a mechanism-guided approach. The best inhibitor shows efficient inhibitory activity against H. pylori (IC 50 = 1.8 ± 0.4 μM) and identifies MqnE as a promising target for antibiotic development.

Original languageEnglish (US)
Pages (from-to)363-366
Number of pages4
JournalACS Medicinal Chemistry Letters
Volume10
Issue number3
DOIs
StatePublished - Mar 14 2019

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Vitamin K 2
Biosynthesis
Pylorus
Anti-Bacterial Agents
Enzymes
futalosine

Keywords

  • antibiotic
  • bisubstrate inhibitor
  • Helicobacter pylori
  • MqnE
  • Radical SAM enzyme

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Cite this

Antibacterial Strategy against H. pylori : Inhibition of the Radical SAM Enzyme MqnE in Menaquinone Biosynthesis. / Joshi, Sumedh; Fedoseyenko, Dmytro; Mahanta, Nilkamal; Ducati, Rodrigo G.; Feng, Mu; Schramm, Vern L.; Begley, Tadhg P.

In: ACS Medicinal Chemistry Letters, Vol. 10, No. 3, 14.03.2019, p. 363-366.

Research output: Contribution to journalArticle

Joshi, Sumedh ; Fedoseyenko, Dmytro ; Mahanta, Nilkamal ; Ducati, Rodrigo G. ; Feng, Mu ; Schramm, Vern L. ; Begley, Tadhg P. / Antibacterial Strategy against H. pylori : Inhibition of the Radical SAM Enzyme MqnE in Menaquinone Biosynthesis. In: ACS Medicinal Chemistry Letters. 2019 ; Vol. 10, No. 3. pp. 363-366.
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