Identification of a Mycothiol-Dependent Nitroreductase from Mycobacterium tuberculosis

ACS Infectious Diseases
Ana NegriSelin Somersan-Karakaya

Abstract

The success of Mycobacterium tuberculosis (Mtb) as a pathogen depends on the redundant and complex mechanisms it has evolved for resisting nitrosative and oxidative stresses inflicted by host immunity. Improving our understanding of these defense pathways can reveal vulnerable points in Mtb pathogenesis. In this study, we combined genetic, structural, computational, biochemical, and biophysical approaches to identify a novel enzyme class represented by Rv2466c. We show that Rv2466c is a mycothiol-dependent nitroreductase of Mtb and can reduce the nitro group of a novel mycobactericidal compound using mycothiol as a cofactor. In addition to its function as a nitroreductase, Rv2466c confers partial protection to menadione stress.

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Citations

Feb 23, 2019·The Journal of Experimental Medicine·Lucía PiacenzaRafael Radi
Nov 13, 2019·Cell Chemical Biology·Xin WangJoel S Freundlich
Mar 5, 2021·Frontiers in Veterinary Science·Rachel MizziKarren M Plain
Nov 16, 2019·ACS Infectious Diseases·Laurent R ChiarelliMaria Rosalia Pasca

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Datasets Mentioned

BETA
AAK46370.1

Methods Mentioned

BETA
PCR
PCRs
protein assay
size-exclusion chromatography

Software Mentioned

Chimera
PhyML
Profinder
LigPrep Preparation Wizard
CovDock
iTASSER
Hit
BLAST
CCP4
CD

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