Tuning of Peroxiredoxin Catalysis for Various Physiological Roles

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  • Peroxiredoxins (Prxs) make up an ancient family of enzymes that are the predominant peroxidases for nearly all organisms and play essential roles in reducing hydrogen peroxide, organic hydroperoxides, and peroxynitrite. Even between distantly related organisms, the core protein fold and key catalytic residues related to its cysteine-based catalytic mechanism have been retained. Given that these enzymes appeared early in biology, Prxs have experienced over a billion years of optimization for specific ecological niches. Although their basic enzymatic function remains the same, Prxs have diversified and are involved in roles such as protecting DNA against mutation, defending pathogens against host immune responses, suppressing tumor formation, and—for eukaryotes—helping regulate peroxide signaling via hyperoxidation of their catalytic Cys. Here, we review the current understanding of the physiological roles of Prxs by analyzing knockout and knockdown studies from ca. twenty-five different species. We also review what is known about the structural basis for the sensitivity of some eukaryotic Prxs to inactivation by hyperoxidation. In considering the physiological relevance of hyperoxidation, we explore the distribution across species of sulfiredoxin (Srx), the enzyme responsible for rescuing hyperoxidized Prxs. We unexpectedly find that among eukaryotes appearing to have a “sensitive” Prx isoform, some do not contain Srx. Also, as Prxs are suggested to be promising targets for drug design, we discuss the rationale behind recently proposed strategies for their selective inhibition.
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  • Perkins, A., Poole, L. B., & Karplus, P. A. (2014). Tuning of Peroxiredoxin Catalysis for Various Physiological Roles. Biochemistry, 53(49), 7693-7705. doi:10.1021/bi5013222
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  • 53
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  • 49
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  • This work was made possible by funding from National Institutes of Health grant RO1 GM050389 to L.B.P. and P.A.K.



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