Hyperoxidation of Peroxiredoxin 6 Induces Alteration from Dimeric to Oligomeric State

Antioxidants

RimpyKaur Chowhan¹  Laishram Rajendrakumar Singh¹  Pushpa Kakchingtabam²  Khundrakpam Herojit Singh²  Sharifun Shahnaj²  Potshangbam Nongdam²  Hamidur Rahaman²  PotshangbamAngamba Meetei²  AronB. Fisher³ 

[1] ACBR, Delhi University, New Delhi, Delhi 110022, India;Department of Biotechnology, Manipur University, Manipur 795003, India;Institute for Environmental Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104-6068, USA;

关键词: peroxidatic cysteine;    thioredoxin fold;    sulfonic/sulfinic acid;    phospholipase A2 activity;    reactive oxygen species;   

DOI  :  10.3390/antiox8020033

来源: DOAJ

【 摘 要 】

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 (C_p) 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.

【 授权许可】

Unknown