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Radioprotective Role of Peroxiredoxin 6
Open AccessArticle

Hyperoxidation of Peroxiredoxin 6 Induces Alteration from Dimeric to Oligomeric State

1
Department of Biotechnology, Manipur University, Manipur 795003, India
2
ACBR, Delhi University, New Delhi, Delhi 110022, India
3
Institute for Environmental Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104-6068, USA
*
Author to whom correspondence should be addressed.
Antioxidants 2019, 8(2), 33; https://doi.org/10.3390/antiox8020033
Received: 30 November 2018 / Revised: 22 January 2019 / Accepted: 29 January 2019 / Published: 2 February 2019
(This article belongs to the Special Issue Peroxiredoxin 6 as a Unique Member of the Peroxiredoxin Family)
Peroxiredoxins(Prdx), the family of non-selenium glutathione peroxidases, are important antioxidant enzymes that defend our system from the toxic reactive oxygen species (ROS). They are thiol-based peroxidases that utilize self-oxidation of their peroxidatic cysteine (Cp) group to reduce peroxides and peroxidized biomolecules. However, because of its high affinity for hydrogen peroxide this peroxidatic cysteine moiety is extremely susceptible to hyperoxidation, forming peroxidase inactive sulfinic acid (Cys-SO2H) and sulfonic acid (Cys-SO3H) derivatives. With the exception of peroxiredoxin 6 (Prdx6), hyperoxidized sulfinic forms of Prdx can be reversed to restore peroxidase activity by the ATP-dependent enzyme sulfiredoxin. Interestingly, hyperoxidized Prdx6 protein seems to have physiological significance as hyperoxidation has been reported to dramatically upregulate its calcium independent phospholipase A2 activity. Using biochemical studies and molecular dynamic (MD) simulation, we investigated the roles of thermodynamic, structural and internal flexibility of Prdx6 to comprehend the structural alteration of the protein in the oxidized state. We observed the loosening of the hydrophobic core of the enzyme in its secondary and tertiary structures. These changes do not affect the internal dynamics of the protein (as indicated by root-mean-square deviation, RMSD and root mean square fluctuation, RMSF plots). Native-PAGE and dynamic light scattering experiments revealed the formation of higher oligomers of Prdx6 under hyperoxidation. Our study demonstrates that post translational modification (like hyperoxidation) in Prdx6 can result in major alterations of its multimeric status. View Full-Text
Keywords: peroxidatic cysteine; thioredoxin fold; sulfonic/sulfinic acid; phospholipase A2 activity; reactive oxygen species peroxidatic cysteine; thioredoxin fold; sulfonic/sulfinic acid; phospholipase A2 activity; reactive oxygen species
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Shahnaj, S.; Chowhan, R.K.; Meetei, P.A.; Kakchingtabam, P.; Herojit Singh, K.; Rajendrakumar Singh, L.; Nongdam, P.; Fisher, A.B.; Rahaman, H. Hyperoxidation of Peroxiredoxin 6 Induces Alteration from Dimeric to Oligomeric State. Antioxidants 2019, 8, 33.

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