Effect of dimerization of peroxiredoxin 6 on its enzymatic activities (739.4)

Abstract

Peroxiredoxin 6 (Prdx6) is a unique non‐seleno 1‐Cys protein with both peroxidase and phospholipase A2 (PLA2) activities. It is highly expressed in the lung where it plays an important role in antioxidant defense and lung surfactant metabolism. Glutathionylation of Prdx6 mediated by πGST is required for its peroxidatic catalytic cycle while its PLA2 activity is enhanced by the presence of GSH. The crystal structure of human Prdx6 reveals a dimer with discrete domains for each activity in each monomer. The N‐terminal domain has a thioredoxin fold and the C‐terminal domain functions in dimerization. We hypothesize that dimerization of Prdx6 might play an important role in its enzymatic activities and have predicted that amino acid residues L145 and L148 are important for protein dimerization. By analytical ultracentrifugation, protein mutated at L145/148 unlike wild type did not dimerize. Peroxidase activity was dramatically reduced by mutation at either of these sites and abolished by double mutation. However, these mutations had no effect on PLA2 activity. Therefore, the dimerization of Prdx6 plays an important role for its peroxidase but not its PLA2 activity.Grant Funding Source: Supported by NIH grants HL102016 and HL19737