2. Academic Validation
  3. Identification of a Mycothiol-Dependent Nitroreductase from Mycobacterium tuberculosis

Identification of a Mycothiol-Dependent Nitroreductase from Mycobacterium tuberculosis

  • ACS Infect Dis. 2018 May 11;4(5):771-787. doi: 10.1021/acsinfecdis.7b00111.
Ana Negri 1,  Prisca Javidnia 2,  Ran Mu,  Xiaojie Zhang,  Jeremie Vendome 1,  Ben Gold,  Julia Roberts,  Dipti Barman,  Thomas Ioerger,  James C Sacchettini,  Xiuju Jiang,  Kristin Burns-Huang,  Thulasi Warrier,  Yan Ling,  J David Warren,  Deena A Oren 3,  Thijs Beuming 1,  Hongyao Wang,  Jie Wu,  Haitao Li,  Kyu Y Rhee 2,  Carl F Nathan,  Gang Liu,  Selin Somersan-Karakaya 2
Affiliations

Affiliations

  • 1 Schrödinger, Inc. , 120 West 45th Street , New York , New York 10036 , United States.
  • 2 Department of Medicine, Division of Infectious Diseases , Weill Cornell Medical College , 1300 York Avenue , New York , New York 10065 , United States.
  • 3 Structural Biology Resource Center , Rockefeller University , 1230 York Avenue , New York , New York 10065 , United States.
PMID: 29465985 DOI: 10.1021/acsinfecdis.7b00111
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.

Keywords

Mycobacterium tuberculosis; Rv2466c; menadione; mrx-2; mycothiol; nitrofuranylcalanolide; nitroreductase; oxidoreductase.

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