title: The AhpC and AhpD antioxidant defense system of Mycobacterium tuberculosis.
abstract: The peroxiredoxin AhpC from Mycobacterium tuberculosis has been expressed, purified, and characterized. It differs from other well characterized AhpC proteins in that it has three rather than one or two cysteine residues. Mutagenesis studies show that all three cysteine residues are important for catalytic activity. Analysis of the M. tuberculosis genome identified a second protein, AhpD, which has no sequence identity with AhpC but is under the control of the same promoter. This protein has also been cloned, expressed, purified, and characterized. AhpD, which has only been identified in the genomes of mycobacteria and Streptomyces viridosporus, is shown here to also be an alkylhydroperoxidase. The endogenous electron donor for catalytic turnover of the two proteins is not known, but both can be turned over with AhpF from Salmonella typhimurium or, particularly in the case of AhpC, with dithiothreitol. AhpC and AhpD reduce alkylhydroperoxides more effectively than H(2)O(2) but do not appear to interact with each other. These two proteins appear to be critical elements of the antioxidant defense system of M. tuberculosis and may be suitable targets for the development of novel anti-tuberculosis strategies.
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, California 94143-0446, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Hillas
authors.forename: F S
authors.initials: FS
authors.lastname: del Alba
authors.forename: J
authors.initials: J
authors.lastname: Oyarzabal
authors.forename: A
authors.initials: A
authors.lastname: Wilks
authors.forename: P R
authors.initials: PR
authors.lastname: Ortiz De Montellano
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D001483:Base Sequence; D002384:Catalysis; D017931:DNA Primers; D004229:Dithiothreitol / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000737:chemistry / Q000378:metabolism*; D054464:Peroxiredoxins; D011487:Protein Conformation; D013379:Substrate Specificity
chemical_list: D000975:Antioxidants; D001426:Bacterial Proteins; D017931:DNA Primers; D010544:Peroxidases; D054464:Peroxiredoxins; D004229:Dithiothreitol