Reduction of 1-Cys peroxiredoxins by ascorbate changes the thiol-specific antioxidant paradigm, revealing another function of vitamin C.
Peroxiredoxins (Prx) are widely distributed peroxidases that can be divided into 1-Cys and 2-Cys Prx groups based on the number of conserved cysteine residues that participate in their catalytical cycle. Prx have been described to be strictly dependent on thiols, but here, we show that ascorbate (vitamin C) also reduces 1-Cys Prx, but not 2-Cys Prx, from several taxonomic groups. Reduction by ascorbate is partly related to the fact that the oxidized form of 1-Cys Prx is a stable sulfenic acid (Cys-SOH) instead of a disulfide. In addition, a histidine residue in the active site is required. In fact, we engineered a 2-Cys Prx with these two features, and it displayed ascorbate peroxidase activity. These data represent a breakthrough in the thiol-specific antioxidant paradigm. Ascorbate may be the long-sought-after biological reductant of 1-Cys Prx. Because ascorbate is present in high amounts in cells, the ascorbate/protein sulfenic acid pair represents an aspect of redox biochemistry that has yet to be explored in vivo.
Monteiro
Gisele
G
Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, Rua do Matão 277, CEP 05508-900, São Paulo, Brazil.
Horta
Bruno B
BB
Pimenta
Daniel Carvalho
DC
Augusto
Ohara
O
Netto
Luis E S
LE
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D060387:Ascorbate Peroxidases; D001205:Ascorbic Acid / Q000378:metabolism*; D002384:Catalysis; D004229:Dithiothreitol; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000378:metabolism*; D054464:Peroxiredoxins; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D000596:Amino Acids; D000975:Antioxidants; D029701:Saccharomyces cerevisiae Proteins; D013438:Sulfhydryl Compounds; C410041:PRX1 protein, S cerevisiae; D010544:Peroxidases; D060387:Ascorbate Peroxidases; D054464:Peroxiredoxins; D001205:Ascorbic Acid; D004229:Dithiothreitol