Reduction of peroxides and dinitrobenzenes by Mycobacterium tuberculosis thioredoxin and thioredoxin reductase.
The thioredoxin (Trx) and thioredoxin reductase (TR) of Mycobacterium tuberculosis have been expressed in Escherichia coli and shown to reduce peroxides and dinitrobenzenes. The reduction of H2O2 requires both Trx and TR and is more efficient under anaerobic than aerobic conditions. In contrast, cumene hydroperoxide is reduced to cumyl alcohol and acetophenone in a process that requires NADPH and TR but not Trx. Cumene hydroperoxide reduction is partially inhibited by chelation of trace metals in the medium. The reduction of cumene hydroperoxide by TR is more effective under anaerobic than aerobic conditions due to a competing oxidase reaction in which electrons are transferred from TR to O2. Under anaerobic conditions, dinitrobenzenes also serve as electron acceptors and are reduced by TR to nitroanilines, but the enzyme does not reduce mononitrobenzenes or mononitroimidazoles such as metronidazole. The reductive activity of the Trx-TR system may modify the antioxidant defenses of M. tuberculosis.
Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco 94143-0446, USA.
Z
Z
Zhang
P J
PJ
Hillas
P R
PR
Ortiz de Montellano
D001555:Benzene Derivatives / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004136:Dinitrobenzenes / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D016877:Oxidants / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D010545:Peroxides / Q000378:metabolism*; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism*; D013879:Thioredoxins / Q000378:metabolism*; D020122:tert-Butylhydroperoxide / Q000378:metabolism
D001555:Benzene Derivatives; D004136:Dinitrobenzenes; D005609:Free Radicals; D016877:Oxidants; D010545:Peroxides; D013879:Thioredoxins; D020122:tert-Butylhydroperoxide; D006861:Hydrogen Peroxide; D013880:Thioredoxin-Disulfide Reductase; C007164:cumene hydroperoxide