Structural and functional diversity of the Peroxiredoxin 6 enzyme family.

Peroxiredoxins (Prdxs) with a single peroxidative cysteine (Cp) in a conserved motif PXXX(T/S)XXCp within its thioredoxin fold, have been classified as the Prdx6 family. The single CP of Peroxiredoxin 6 (Prdx6) uses various external electron donors including glutathione, thioredoxin, and ascorbic acid for its peroxidase activity. Prdx6 proteins also exhibit Ca2+-independent phospholipase A2 (PLA2), lysophosphosphatidylcholine acyltransferase (LPCAT), and chaperone activities depending on cellular localization and the oxidation and oligomerisation states of the protein. Although there are wide variations in both the structure and function of the Prdx6 family members in various organisms and under varying physiological conditions, all Prdx6 proteins show the unique structural trait of a long C-terminal extension that is also seen in Prdx1, but not in other members of the Prdx family. Physiologically, Prdx6s play important roles in: protection against oxidative stress, cell membrane repair, mammalian lung surfactant turnover, activation of some nicotinamide adenine dinucleotide phosphate oxidases (NADPH oxidases types 1 and 2), and in regulation of seed germination in plants. Of crucial importance will be further evaluation of the role of Prdx6 enzymes in cancer spread and metastasis.This review describes the unique structural features of Prdx6 enzymes that are associated with its multifunctional physiological activities.

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