Title | Identification of a Mycothiol-Dependent Nitroreductase from Mycobacterium tuberculosis. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Negri 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 C, Liu G, Somersan-Karakaya S |
Journal | ACS Infect Dis |
Volume | 4 |
Issue | 5 |
Pagination | 771-787 |
Date Published | 2018 05 11 |
ISSN | 2373-8227 |
Keywords | Animals, Bacterial Proteins, Binding Sites, Cysteine, Disease Models, Animal, Enzyme Activation, Female, Glycopeptides, Inositol, Mice, Models, Molecular, Mutation, Mycobacterium tuberculosis, Nitroreductases, Oxidation-Reduction, Oxidative Stress, Phylogeny, Protein Binding, Protein Conformation, Structure-Activity Relationship, Tuberculosis |
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. |
DOI | 10.1021/acsinfecdis.7b00111 |
Alternate Journal | ACS Infect Dis |
PubMed ID | 29465985 |
PubMed Central ID | PMC5952258 |
Grant List | K08 AI108799 / AI / NIAID NIH HHS / United States |
Submitted by dwd2001 on November 9, 2018 - 11:43am