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Identification of a Mycothiol-Dependent Nitroreductase from Mycobacterium tuberculosis.

TitleIdentification of a Mycothiol-Dependent Nitroreductase from Mycobacterium tuberculosis.
Publication TypeJournal Article
Year of Publication2018
AuthorsNegri A, Javidnia P, Mu R, Zhang X, Vendome J, Gold B, Roberts J, Barman D, Ioerger T, Sacchettini JC, Jiang X, Burns-Huang K, Warrier T, Ling Y, J Warren D, Oren DA, Beuming T, Wang H, Wu J, Li H, Rhee KY, Nathan CF, Liu G, Somersan-Karakaya S
JournalACS Infect Dis
Volume4
Issue5
Pagination771-787
Date Published2018 May 11
ISSN2373-8227
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.

DOI10.1021/acsinfecdis.7b00111
Alternate JournalACS Infect Dis
PubMed ID29465985
PubMed Central IDPMC5952258
Grant ListK08 AI108799 / AI / NIAID NIH HHS / United States

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