Abstract
Glutathione (GSH) peroxidases (GPxs or GSHPx) and thioredoxin (Trx) peroxidases (TPxs) are two classes of peroxidases that catalyze the reduction of peroxides. GPxs and TPxs generally use GSH or Trx, respectively, to recycle the oxidized cysteine (Cys) residue in the protein. However, it is unclear why unlike human GPxs, the Schizosaccharomyces pombe Gpx1 (spGpx1) prefers Trx over GSH for recycling of the active-site peroxidatic Cys residue. Here, we compared spGpx1 and S. pombe Tpx1 (spTpx1) protein sequences with those of their respective homologs in Saccharomyces cerevisiae and humans. Our analysis revealed that like spTpx1, spGpx1 contains a pair of conserved Cys residues (Cys36 and Cys82). These two conserved Cys residues are named peroxidatic and resolving Cys residues, respectively, and are found only in GPxs and TPxs that prefer Trx as an electron donor. Our analysis suggested that Cys36 and Cys82 in spGpx1 are most likely to form a disulfide bond upon oxidation of Cys36. Molecular modelling predicted that a conformational change might be required for the formation of this disulfide bond. Evolutionary analysis suggested that fungal GPxs and TPxs are related by divergent evolution from a common ancestor. Our analyses support a prediction that while spGpx1 and spTpx1 are phylogenetically and functionally different, they evolved from a common ancestor and use a similar mechanism for recycling of the active-site peroxidatic Cys residue.