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

doi:10.1021/acsmedchemlett.8b00649

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 journal › Article › peer-review

13 Scopus citations

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 (IC₅₀ = 1.8 ± 0.4 μM) and identifies MqnE as a promising target for antibiotic development.

Original language	English (US)
Pages (from-to)	363-366
Number of pages	4
Journal	ACS Medicinal Chemistry Letters
Volume	10
Issue number	3
DOIs	https://doi.org/10.1021/acsmedchemlett.8b00649
State	Published - Mar 14 2019

Keywords

Helicobacter pylori
MqnE
Radical SAM enzyme
antibiotic
bisubstrate inhibitor

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

Access to Document

10.1021/acsmedchemlett.8b00649

Cite this

@article{eda6de1ada6546ecb4b0d466d22b750b,

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

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 (IC50 = 1.8 ± 0.4 μM) and identifies MqnE as a promising target for antibiotic development.",

keywords = "Helicobacter pylori, MqnE, Radical SAM enzyme, antibiotic, bisubstrate inhibitor",

author = "Sumedh Joshi and Dmytro Fedoseyenko and Nilkamal Mahanta and Ducati, {Rodrigo G.} and Mu Feng and Schramm, {Vern L.} and Begley, {Tadhg P.}",

note = "Publisher Copyright: {\textcopyright} 2019 American Chemical Society.",

year = "2019",

month = mar,

day = "14",

doi = "10.1021/acsmedchemlett.8b00649",

language = "English (US)",

volume = "10",

pages = "363--366",

journal = "ACS Medicinal Chemistry Letters",

issn = "1948-5875",

publisher = "American Chemical Society",

number = "3",

}

TY - JOUR

T1 - Antibacterial Strategy against H. pylori

T2 - Inhibition of the Radical SAM Enzyme MqnE in Menaquinone Biosynthesis

AU - Joshi, Sumedh

AU - Fedoseyenko, Dmytro

AU - Mahanta, Nilkamal

AU - Ducati, Rodrigo G.

AU - Feng, Mu

AU - Schramm, Vern L.

AU - Begley, Tadhg P.

PY - 2019/3/14

Y1 - 2019/3/14

N2 - 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 (IC50 = 1.8 ± 0.4 μM) and identifies MqnE as a promising target for antibiotic development.

AB - 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 (IC50 = 1.8 ± 0.4 μM) and identifies MqnE as a promising target for antibiotic development.

KW - Helicobacter pylori

KW - MqnE

KW - Radical SAM enzyme

KW - antibiotic

KW - bisubstrate inhibitor

UR - http://www.scopus.com/inward/record.url?scp=85062320599&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062320599&partnerID=8YFLogxK

U2 - 10.1021/acsmedchemlett.8b00649

DO - 10.1021/acsmedchemlett.8b00649

M3 - Article

AN - SCOPUS:85062320599

SN - 1948-5875

VL - 10

SP - 363

EP - 366

JO - ACS Medicinal Chemistry Letters

JF - ACS Medicinal Chemistry Letters

IS - 3

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this