Peroxiredoxin 5: structure, mechanism, and function of the mammalian atypical 2-Cys peroxiredoxin.
Peroxiredoxin 5 (PRDX5) was the last member to be identified among the six mammalian peroxiredoxins. It is also the unique atypical 2-Cys peroxiredoxin in mammals. Like the other five members, PRDX5 is widely expressed in tissues but differs by its surprisingly large subcellular distribution. In human cells, it has been shown that PRDX5 can be addressed to mitochondria, peroxisomes, the cytosol, and the nucleus. PRDX5 is a peroxidase that can use cytosolic or mitochondrial thioredoxins to reduce alkyl hydroperoxides or peroxynitrite with high rate constants in the 10(6) to 10(7) M(-1)s(-1) range, whereas its reaction with hydrogen peroxide is more modest, in the 10(5) M(-1)s(-1) range. PRDX5 crystal structures confirmed the proposed enzymatic mechanisms based on biochemical data but revealed also some specific unexpected structural features. So far, PRDX5 has been viewed mainly as a cytoprotective antioxidant enzyme acting against endogenous or exogenous peroxide attacks rather than as a redox sensor. Accordingly, overexpression of the enzyme in different subcellular compartments protects cells against death caused by nitro-oxidative stresses, whereas gene silencing makes them more vulnerable. Thus, more than 10 years after its molecular cloning, mammalian PRDX5 appears to be a unique peroxiredoxin exhibiting specific functional and structural features.
Knoops
Bernard
B
Institut des Sciences de Vie, Université catholique de Louvain, Louvain-la-Neuve, Belgium. bernard.knoops@uclouvain.be
Goemaere
Julie
J
Van der Eecken
Valérie
V
Declercq
Jean-Paul
JP
D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000737:chemistry*; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008969:Molecular Sequence Data; D054464:Peroxiredoxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D006861:Hydrogen Peroxide; C504194:2-cys peroxiredoxin, human; C515974:PRDX5 protein, human; D054464:Peroxiredoxins; D003545:Cysteine