[en] The peroxiredoxins define an emerging family of peroxidases able to reduce hydrogen peroxide and alkyl hydroperoxides with the use of reducing equivalents derived from thiol-containing donor molecules such as thioredoxin, glutathione, trypanothione and AhpF. Peroxiredoxins have been identified in prokaryotes as well as in eukaryotes. Peroxiredoxin 5 (PRDX5) is a novel type of mammalian thioredoxin peroxidase widely expressed in tissues and located cellularly to mitochondria, peroxisomes and cytosol. Functionally, PRDX5 has been implicated in antioxidant protective mechanisms as well as in signal transduction in cells. We report here the 1.5 Ǻ resolution crystal structure of human PRDX5 in its reduced form. The crystal structure reveals that PRDX5 presents a thioredoxin-like domain. Interestingly, the crystal structure shows also that PRDX5 does not form a dimer like other mammalian members of the peroxiredoxin family. In the reduced form of PRDX5, Cys47 and Cys151 are distant of 13.8 Ǻ although these two cysteine residues are thought to be involved in peroxide reductase activity by forming an intramolecular disul®de 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 benzoate 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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Declercq, Jean-Paul; Université Catholique de Louvain - UCL > Département de Chimie > Unité de Chimie Structurale (CSTR)
Evrard, Christine ; Université Catholique de Louvain - UCL > Département de Chimie > Unité de Chimie Structurale (CSTR)
Clippe, André; Université Catholique de Louvain - UCL
Vander Stricht, Delphine; Université Catholique de Louvain - UCL
Bernard, Alfred; Université Catholique de Louvain - UCL
Knoops, Bernard; Université Catholique de Louvain - UCL
Language :
English
Title :
Crystal Structure of Human Peroxiredoxin 5, a Novel Type of Mammalian Peroxiredoxin at 1.5 Ǻ Resolution
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