Download MendeleyIdentification of a Mycothiol-Dependent Nitroreductase from Mycobacterium tuberculosis.
Negri, A., Javidnia, P., Mu, R., Zhang, X., Vendome, J., Gold, B., Roberts, J., Barman, D., Ioerger, T., Sacchettini, J.C., Jiang, X., Burns-Huang, K., Warrier, T., Ling, Y., Warren, J.D., Oren, D.A., Beuming, T., Wang, H., Wu, J., Li, H., Rhee, K.Y., Nathan, C.F., Liu, G., Somersan-Karakaya, S.(2018) ACS Infect Dis 4: 771-787
- PubMed: 29465985
- DOI: https://doi.org/10.1021/acsinfecdis.7b00111
- Primary Citation of Related Structures:
5XUR - PubMed 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.
Organizational Affiliation:
Schrödinger, Inc. , 120 West 45th Street , New York , New York 10036 , United States.
