Structural Changes Upon Peroxynitrite-mediated Nitration of Peroxiredoxin 2; Nitrated Prx2 Resembles Its Disulfide-oxidized Form

Overview

Journal Arch Biochem Biophys

Publisher Elsevier

Specialties Biochemistry
Biophysics

Date 2015 Nov 28

PMID 26612102

Citations 9

Authors

Lia Randall

Bruno Manta

Kimberly J Nelson

Javier Santos

Leslie B Poole

Ana Denicola

Affiliations

Soon will be listed here.

Abstract

Peroxiredoxins are cys-based peroxidases that function in peroxide detoxification and H2O2-induced signaling. Human Prx2 is a typical 2-Cys Prx arranged as pentamers of head-to-tail homodimers. During the catalytic mechanism, the active-site cysteine (CP) cycles between reduced, sulfenic and disulfide state involving conformational as well as oligomeric changes. Several post-translational modifications were shown to affect Prx activity, in particular CP overoxidation which leads to inactivation. We have recently reported that nitration of Prx2, a post-translational modification on non-catalytic tyrosines, unexpectedly increases its peroxidase activity and resistance to overoxidation. To elucidate the cross-talk between this post-translational modification and the enzyme catalysis, we investigated the structural changes of Prx2 after nitration. Analytical ultracentrifugation, UV absorption, circular dichroism, steady-state and time-resolved fluorescence were used to connect catalytically relevant redox changes with tyrosine nitration. Our results show that the reduced nitrated Prx2 structurally resembles the disulfide-oxidized native form of the enzyme favoring a locally unfolded conformation that facilitates disulfide formation. These results provide structural basis for the kinetic analysis previously reported, the observed increase in activity and the resistance to overoxidation of the peroxynitrite-treated enzyme.

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References

Veal E, Day A, Morgan B . Hydrogen peroxide sensing and signaling. Mol Cell. 2007; 26(1):1-14. DOI: 10.1016/j.molcel.2007.03.016. View

Seidel T, Seefeldt B, Sauer M, Dietz K . In vivo analysis of the 2-Cys peroxiredoxin oligomeric state by two-step FRET. J Biotechnol. 2010; 149(4):272-9. DOI: 10.1016/j.jbiotec.2010.06.016. View

Yang K, Kang S, Woo H, Hwang S, Chae H, Kim K . Inactivation of human peroxiredoxin I during catalysis as the result of the oxidation of the catalytic site cysteine to cysteine-sulfinic acid. J Biol Chem. 2002; 277(41):38029-36. DOI: 10.1074/jbc.M206626200. View

Trujillo M, Ferrer-Sueta G, Radi R . Peroxynitrite detoxification and its biologic implications. Antioxid Redox Signal. 2008; 10(9):1607-20. DOI: 10.1089/ars.2008.2060. View

Matsumura T, Okamoto K, Iwahara S, Hori H, Takahashi Y, Nishino T . Dimer-oligomer interconversion of wild-type and mutant rat 2-Cys peroxiredoxin: disulfide formation at dimer-dimer interfaces is not essential for decamerization. J Biol Chem. 2007; 283(1):284-293. DOI: 10.1074/jbc.M705753200. View

Hall A, Nelson K, Poole L, Karplus P . Structure-based insights into the catalytic power and conformational dexterity of peroxiredoxins. Antioxid Redox Signal. 2010; 15(3):795-815. PMC: 3125576. DOI: 10.1089/ars.2010.3624. View

Fang J, Nakamura T, Cho D, Gu Z, Lipton S . S-nitrosylation of peroxiredoxin 2 promotes oxidative stress-induced neuronal cell death in Parkinson's disease. Proc Natl Acad Sci U S A. 2007; 104(47):18742-7. PMC: 2141847. DOI: 10.1073/pnas.0705904104. View

Flohe L . Changing paradigms in thiology from antioxidant defense toward redox regulation. Methods Enzymol. 2010; 473:1-39. DOI: 10.1016/S0076-6879(10)73001-9. View

Fomenko D, Koc A, Agisheva N, Jacobsen M, Kaya A, Malinouski M . Thiol peroxidases mediate specific genome-wide regulation of gene expression in response to hydrogen peroxide. Proc Natl Acad Sci U S A. 2011; 108(7):2729-34. PMC: 3041109. DOI: 10.1073/pnas.1010721108. View

10.

Qu D, Rashidian J, Mount M, Aleyasin H, Parsanejad M, Lira A . Role of Cdk5-mediated phosphorylation of Prx2 in MPTP toxicity and Parkinson's disease. Neuron. 2007; 55(1):37-52. DOI: 10.1016/j.neuron.2007.05.033. View

11.

Romero N, Radi R, Linares E, Augusto O, Detweiler C, Mason R . Reaction of human hemoglobin with peroxynitrite. Isomerization to nitrate and secondary formation of protein radicals. J Biol Chem. 2003; 278(45):44049-57. DOI: 10.1074/jbc.M305895200. View

12.

Jang H, Lee K, Chi Y, Jung B, Park S, Park J . Two enzymes in one; two yeast peroxiredoxins display oxidative stress-dependent switching from a peroxidase to a molecular chaperone function. Cell. 2004; 117(5):625-35. DOI: 10.1016/j.cell.2004.05.002. View

13.

Manta B, Hugo M, Ortiz C, Ferrer-Sueta G, Trujillo M, Denicola A . The peroxidase and peroxynitrite reductase activity of human erythrocyte peroxiredoxin 2. Arch Biochem Biophys. 2008; 484(2):146-54. DOI: 10.1016/j.abb.2008.11.017. View

14.

Morinaka A, Funato Y, Uesugi K, Miki H . Oligomeric peroxiredoxin-I is an essential intermediate for p53 to activate MST1 kinase and apoptosis. Oncogene. 2011; 30(40):4208-18. DOI: 10.1038/onc.2011.139. View

15.

Sarma G, Nickel C, Rahlfs S, Fischer M, Becker K, Karplus P . Crystal structure of a novel Plasmodium falciparum 1-Cys peroxiredoxin. J Mol Biol. 2005; 346(4):1021-34. DOI: 10.1016/j.jmb.2004.12.022. View

16.

Lee W, Choi K, Riddell J, Ip C, Ghosh D, Park J . Human peroxiredoxin 1 and 2 are not duplicate proteins: the unique presence of CYS83 in Prx1 underscores the structural and functional differences between Prx1 and Prx2. J Biol Chem. 2007; 282(30):22011-22. DOI: 10.1074/jbc.M610330200. View

17.

Rhee S, Chae H, Kim K . Peroxiredoxins: a historical overview and speculative preview of novel mechanisms and emerging concepts in cell signaling. Free Radic Biol Med. 2005; 38(12):1543-52. DOI: 10.1016/j.freeradbiomed.2005.02.026. View

18.

Jang H, Kim S, Park S, Jeon H, Lee Y, Jung J . Phosphorylation and concomitant structural changes in human 2-Cys peroxiredoxin isotype I differentially regulate its peroxidase and molecular chaperone functions. FEBS Lett. 2005; 580(1):351-5. DOI: 10.1016/j.febslet.2005.12.030. View

19.

Wood Z, Poole L, Karplus P . Peroxiredoxin evolution and the regulation of hydrogen peroxide signaling. Science. 2003; 300(5619):650-3. DOI: 10.1126/science.1080405. View

20.

Perkins A, Nelson K, Parsonage D, Poole L, Karplus P . Peroxiredoxins: guardians against oxidative stress and modulators of peroxide signaling. Trends Biochem Sci. 2015; 40(8):435-45. PMC: 4509974. DOI: 10.1016/j.tibs.2015.05.001. View