Crystal structure of human peroxiredoxin 5, a novel type of mammalian peroxiredoxin at 1.5 angstrom resolution

The peroxiredoxins define an emerging family of peroxidases able to reduce hydrogen peroxide and alkyl hydroperoxides with the use of reducing equival ents derived from thiol-containing donor molecules such as thioredoxin, glu tathione, trypanothione and AhpF. Peroxiredoxins have been identified in pr okaryotes as well as in eukaryotes. Peroxiredoxin 5 (PRDX5) is a novel type of mammalian thioredoxin peroxidase widely expressed in tissues and locate d cellularly to mitochondria, peroxisomes and cytosol. Functionally, PRDX5 has been implicated in anti, oxidant protective mechanisms as well as in si gnal transduction in cells., We report here the 1.5 Angstrom resolution cry stal structure of human PRDX5 in its reduced form. The crystal structure re veals that PRDX5 presents a thioredoxin-like domain. Interestingly, the cry stal structure shows also that PRDX5 does not form a dimer like other mamma lian members of the peroxiredoxin family. In the reduced form of PRDX5, Cys 47 and Cys151 are distant of 13.8 Angstrom although these two cysteine resi dues are thought to be involved in peroxide reductase activity by forming a n intramolecular disulfide intermediate in the oxidized enzyme. These data suggest that the enzyme would necessitate a conformational change to form a disulfide bond between catalytic Cys47 and Cys151 upon oxidation according to proposed peroxide reduction mechanisms. Moreover, the presence of a ben zoate ion, a hydroxyl radical scavenger, was noted close to the active-site pocket. The possible role of benzoate in the antioxidant activity of PRDX5 is discussed. (C) 2001 Academic Press.