Overview of Peroxiredoxins in Oxidant Defense and Redox Regulation

Leslie B. Poole1, Andrea Hall2, Kimberly J. Nelson1

1 Department of Biochemistry, Wake Forest University School of Medicine, Winston‐Salem, North Carolina, 2 Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon
Publication Name:  Current Protocols in Toxicology
Unit Number:  Unit 7.9
DOI:  10.1002/0471140856.tx0709s49
Online Posting Date:  August, 2011
GO TO THE FULL TEXT: PDF or HTML at Wiley Online Library


Peroxiredoxins are important hydroperoxide detoxification enzymes, yet have only come to the fore in recent years relative to the other major players in peroxide detoxification, heme‐containing catalases and peroxidases and glutathione peroxidases. These cysteine‐dependent peroxidases exhibit high reactivity with hydrogen peroxide, organic hydroperoxides, and peroxynitrite and play major roles not only in peroxide defense, but also in regulating peroxide‐mediated cell signaling. This overview focuses on important peroxiredoxin features that have emerged over the past several decades with an emphasis on catalytic mechanism, regulation, and biological function. Curr. Protoc. Toxicol. 49:7.9.1‐7.9.15. © 2011 by John Wiley & Sons, Inc.

Keywords: peroxidases; antioxidants; antioxidant enzymes; sulfenic acids; hydroperoxides; hydrogen peroxide; thiol peroxidase; Prx; PRDX; redox regulation

PDF or HTML at Wiley Online Library

Table of Contents

  • Introduction
  • Summary
  • Literature Cited
  • Figures
  • Tables
PDF or HTML at Wiley Online Library


PDF or HTML at Wiley Online Library



Literature Cited

   Adimora, N.J., Jones, D.P., and Kemp, M.L. 2010. A model of redox kinetics implicates the thiol proteome in cellular hydrogen peroxide responses. Antioxid. Redox Signal. 13:731‐743.
   Antelmann, H. and Helmann, J.D. 2010. Thiol‐based redox switches and gene regulation. Antioxid Redox Signal. 14:1049‐1063.
   Aran, M., Ferrero, D.S., Pagano, E., and Wolosiuk, R.A. 2009. Typical 2‐Cys peroxiredoxins‐modulation by covalent transformations and noncovalent interactions. Febs J. 276:2478‐2493.
   Baker, L.M. and Poole, L.B. 2003. Catalytic mechanism of thiol peroxidase from Escherichia coli. Sulfenic acid formation and overoxidation of essential CYS61. J. Biol. Chem. 278:9203‐9211.
   Biteau, B., Labarre, J., and Toledano, M.B. 2003. ATP‐dependent reduction of cysteine‐sulphinic acid by S. cerevisiae sulphiredoxin. Nature 425:980‐984.
   Cha, M.K., Kim, H.K., and Kim, I.H. 1995. Thioredoxin‐linked “thiol peroxidase” from periplasmic space of Escherichia coli. J. Biol. Chem. 270:28635‐28641.
   Chae, H.Z., Chung, S.J., and Rhee, S.G. 1994a. Thioredoxin‐dependent peroxide reductase from yeast. J. Biol. Chem. 269:27670‐27678.
   Chae, H.Z., Robison, K., Poole, L.B., Church, G., Storz, G., and Rhee, S.G. 1994b. Cloning and sequencing of thiol‐specific antioxidant from mammalian brain: Alkyl hydroperoxide reductase and thiol‐specific antioxidant define a large family of antioxidant enzymes. Proc. Natl. Acad. Sci. U.S.A. 91:7017‐7021.
   Chang, T.S., Jeong, W., Choi, S.Y., Yu, S., Kang, S.W., and Rhee, S.G. 2002. Regulation of peroxiredoxin I activity by Cdc2‐mediated phosphorylation. J. Biol. Chem. 277:25370‐25376.
   Choi, H.J., Kang, S.W., Yang, C.H., Rhee, S.G., and Ryu, S.E. 1998. Crystal structure of a novel human peroxidase enzyme at 2.0 Å resolution. Nat. Struct. Biol. 5:400‐406.
   Copley, S.D., Novak, W.R., and Babbitt, P.C. 2004. Divergence of function in the thioredoxin fold suprafamily: Evidence for evolution of peroxiredoxins from a thioredoxin‐like ancestor. Biochemistry 43:13981‐13995.
   Cordray, P., Doyle, K., Edes, K., Moos, P.J., and Fitzpatrick, F.A. 2007. Oxidation of 2‐Cys‐peroxiredoxins by arachidonic acid peroxide metabolites of lipoxygenases and cyclooxygenase‐2. J. Biol. Chem. 282:32623‐32629.
   Cox, A.G., Peskin, A.V., Paton, L.N., Winterbourn, C.C., and Hampton, M.B. 2009. Redox potential and peroxide reactivity of human peroxiredoxin 3. Biochemistry 48:6495‐6501.
   Crane, E.J. 3rd, Vervoort, J., and Claiborne, A. 1997. 13C NMR analysis of the cysteine‐sulfenic acid redox center of enterococcal NADH peroxidase. Biochemistry 36:8611‐8618.
   D'Autreaux, B. and Toledano, M.B. 2007. ROS as signalling molecules: Mechanisms that generate specificity in ROS homeostasis. Nat. Rev. Mol. Cell Biol. 8:813‐824.
   Dietz, K.J. 2011. Peroxiredoxins in plants and cyanobacteria. Antioxid. Redox Signal. In press.
   Dubuisson, M., Vander Stricht, D., Clippe, A., Etienne, F., Nauser, T., Kissner, R., Koppenol, W.H., Rees, J.F., and Knoops, B. 2004. Human peroxiredoxin 5 is a peroxynitrite reductase. FEBS Lett. 571:161‐165.
   Ellis, H.R. and Poole, L.B. 1997. Roles for the two cysteine residues of AhpC in catalysis of peroxide reduction by alkyl hydroperoxide reductase from Salmonella typhimurium. Biochemistry 36:13349‐13356.
   Flohé, L. 2010. Changing paradigms in thiology from antioxidant defense toward redox regulation. Methods Enzymol. 473:1‐39.
   Flohé, L., Toppo, S., Cozza, G., and Ursini, F. 2010. A comparison of thiol peroxidase mechanisms. Antioxid. Redox Signal. In press.
   Fomenko, D.E. and Gladyshev, V.N. 2003. Identity and functions of CxxC‐derived motifs. Biochemistry 42:11214‐11225.
   Fomenko, D.E., Marino, S.M., and Gladyshev, V.N. 2008. Functional diversity of cysteine residues in proteins and unique features of catalytic redox‐active cysteines in thiol oxidoreductases. Mol. Cells 26:228‐235.
   Fomenko, D.E., Koc, A., Agisheva, N., Jacobsen, M., Kaya, A., Malinouski, M., Rutherford, J., Siu, K.‐L., Jin, D.‐Y., Winge, D., and Gladyshev, V.N. 2011. Thiol peroxidases mediate specific genome‐wide regulation of gene expression in response to hydrogen peroxide. Proc. Natl. Acad. Sci. U.S.A. In press.
   Forman, H.J., Maiorino, M., and Ursini, F. 2010. Signaling functions of reactive oxygen species. Biochemistry 49:835‐842.
   Fridman, J.S. and Lowe, S.W. 2003. Control of apoptosis by p53. Oncogene 22:9030‐9040.
   Hall, A., Karplus, P.A., and Poole, L.B. 2009. Typical 2‐Cys peroxiredoxins ‐ structures, mechanisms and functions. Febs J. 276:2469‐2477.
   Hall, A., Parsonage, D., Poole, L.B., and Karplus, P.A. 2010. Structural evidence that peroxiredoxin catalytic power is based on transition‐state stabilization. J. Mol. Biol. 402:194‐209.
   Hall, A., Nelson, K., Poole, L., and Karplus, P.A. 2011. Structure‐based insights into the catalytic power and conformational dexterity of peroxiredoxins. Antioxid. Redox Signal. 15:795‐815.
   Hirotsu, S., Abe, Y., Okada, K., Nagahara, N., Hori, H., Nishino, T., and Hakoshima, T. 1999. Crystal structure of a multifunctional 2‐Cys peroxiredoxin heme‐binding protein 23 kDa/proliferation‐associated gene product. Proc. Natl. Acad. Sci. U.S.A. 96:12333‐12338.
   Horta, B.B., de Oliveira, M.A., Discola, K.F., Cussiol, J.R., and Netto, L.E. 2010. Structural and biochemical characterization of peroxiredoxin Qbeta from Xylella fastidiosa: Catalytic mechanism and high reactivity. J. Biol. Chem. 285:16051‐16065.
   Hugo, M., Turell, L., Manta, B., Botti, H., Monteiro, G., Netto, L.E., Alvarez, B., Radi, R., and Trujillo, M. 2009. Thiol and sulfenic acid oxidation of AhpE, the one‐cysteine peroxiredoxin from Mycobacterium tuberculosis: Kinetics, acidity constants, and conformational dynamics. Biochemistry 48:9416‐9426.
   Imlay, J.A. 2008. Cellular defenses against superoxide and hydrogen peroxide. Annu. Rev. Biochem. 77:755‐776.
   Iwao‐Koizumi, K., Matoba, R., Ueno, N., Kim, S.J., Ando, A., Miyoshi, Y., Maeda, E., Noguchi, S., and Kato, K. 2005. Prediction of docetaxel response in human breast cancer by gene expression profiling. J. Clin. Oncol. 23:422‐431.
   Jang, H.H., Lee, K.O., Chi, Y.H., Jung, B.G., Park, S.K., Park, J.H., Lee, J.R., Lee, S.S., Moon, J.C., Yun, J.W., Choi, Y.O., Kim, W.Y., Kang, J.S., Cheong, G.W., Yun, D.J., Rhee, S.G., Cho, M.J., and Lee, S.Y. 2004. Two enzymes in one; two yeast peroxiredoxins display oxidative stress‐dependent switching from a peroxidase to a molecular chaperone function. Cell 117:625‐635.
   Jara, M., Vivancos, A.P., and Hidalgo, E. 2008. C‐terminal truncation of the peroxiredoxin Tpx1 decreases its sensitivity for hydrogen peroxide without compromising its role in signal transduction. Genes Cells 13:171‐179.
   Jeong, W., Cha, M.K., and Kim, I.H. 2000. Thioredoxin‐dependent hydroperoxide peroxidase activity of bacterioferritin comigratory protein (BCP) as a new member of the thiol‐specific antioxidant protein (TSA)/Alkyl hydroperoxide peroxidase C (AhpC) family. J. Biol. Chem. 275:2924‐2930.
   Karplus, P.A. and Hall, A. 2007. Structural survey of the peroxiredoxins. In Peroxiredoxin Systems ( L. Flohé, and J.R. Harris, eds.) pp. 41‐60. Springer, New York.
   Kim, S.K., Yang, J.W., Kim, M.R., Roh, S.H., Kim, H.G., Lee, K.Y., Jeong, H.G., and Kang, K.W. 2008. Increased expression of Nrf2/ARE‐dependent anti‐oxidant proteins in tamoxifen‐resistant breast cancer cells. Free Radic. Biol. Med. 45:537‐546.
   Klomsiri, C., Karplus, P.A., and Poole, L.B. 2010. Cysteine‐based redox switches in enzymes. Antioxid. Redox Signal. 14:1065‐1077.
   Knoops, B., Clippe, A., Bogard, C., Arsalane, K., Wattiez, R., Hermans, C., Duconseille, E., Falmagne, P., and Bernard, A. 1999. Cloning and characterization of AOEB166, a novel mammalian antioxidant enzyme of the peroxiredoxin family. J. Biol. Chem. 274:30451‐30458.
   Knoops, B., Loumaye, E., and Van der Eecken, V. 2007. Evolution of the peroxiredoxins: Taxonomy, homology and characterization. In Peroxiredoxin Systems ( L. Flohé and J.R. Harris, eds.) pp. 27‐40. Springer, New York.
   Koo, K.H., Lee, S., Jeong, S.Y., Kim, E.T., Kim, H.J., Song, K., and Chae, H.‐Z. 2002. Regulation of thioredoxin peroxidase activity by C‐terminal truncation. Arch. Biochem. Biophys. 397:312‐318.
   Koua, D., Cerutti, L., Falquet, L., Sigrist, C.J., Theiler, G., Hulo, N., and Dunand, C. 2009. PeroxiBase: A database with new tools for peroxidase family classification. Nucleic Acids Res. 37:D261‐D266.
   Lee, Y.M., Park, S.H., Shin, D.I., Hwang, J.Y., Park, B., Park, Y.J., Lee, T.H., Chae, H.Z., Jin, B.K., Oh, T.H., and Oh, Y.J. 2008. Oxidative modification of peroxiredoxin is associated with drug‐induced apoptotic signaling in experimental models of Parkinson disease. J. Biol. Chem. 283:9986‐9998.
   Lee, Y.S., Chang, H.W., Jeong, J.E., Lee, S.W., and Kim, S.Y. 2008. Proteomic analysis of two head and neck cancer cell lines presenting different radiation sensitivity. Acta Otolaryngol. 128:86‐92.
   Lehtonen, S.T., Svensk, A.M., Soini, Y., Paakko, P., Hirvikoski, P., Kang, S.W., Saily, M., and Kinnula, V.L. 2004. Peroxiredoxins, a novel protein family in lung cancer. Int. J. Cancer 111:514‐521.
   Li, S., Peterson, N.A., Kim, M.Y., Kim, C.Y., Hung, L.W., Yu, M., Lekin, T., Segelke, B.W., Lott, J.S., and Baker, E.N. 2005. Crystal structure of AhpE from Mycobacterium tuberculosis, a 1‐Cys peroxiredoxin. J. Mol. Biol. 346:1035‐1046.
   Lowther, W.T. and Haynes, A.C. 2011. Reduction of cysteine sulfinic acid in eukaryotic, typical 2‐Cys peroxiredoxins by sulfiredoxin. Antioxid. Redox Signal. In press.
   Manta, B., Hugo, M., Ortiz, C., Ferrer‐Sueta, G., Trujillo, M., and Denicola, A. 2009. The peroxidase and peroxynitrite reductase activity of human erythrocyte peroxiredoxin 2. Arch. Biochem. Biophys. 484:146‐154.
   Moon, J.C., Hah, Y.S., Kim, W.Y., Jung, B.G., Jang, H.H., Lee, J.R., Kim, S.Y., Lee, Y.M., Jeon, M.G., Kim, C.W., Cho, M.J., and Lee, S.Y. 2005. Oxidative stress‐dependent structural and functional switching of a human 2‐Cys peroxiredoxin isotype II that enhances HeLa cell resistance to H2O2‐induced cell death. J. Biol. Chem. 280:28775‐28784.
   Nelson, K.J., Parsonage, D., Hall, A., Karplus, P.A., and Poole, L.B. 2008. Cysteine pKa values for the bacterial peroxiredoxin AhpC. Biochemistry 47:12860‐12868.
   Nelson, K.J., Knutson, S.T., Soito, L., Klomsiri, C., Poole, L.B., and Fetrow, J.S. 2011. Analysis of the peroxiredoxin family: Using active‐site structure and sequence information for global classification and residue analysis. Proteins. In press.
   Neumann, C.A. and Fang, Q. 2007. Are peroxiredoxins tumor suppressors? Curr. Opin. Pharmacol. 7:375‐380.
   Neumann, C.A., Krause, D.S., Carman, C.V., Das, S., Dubey, D.P., Abraham, J.L., Bronson, R.T., Fujiwara, Y., Orkin, S.H., and Van Etten, R.A. 2003. Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression. Nature 424:561‐565.
   Ogusucu, R., Rettori, D., Munhoz, D.C., Soares Netto, L.E., and Augusto, O. 2007. Reactions of yeast thioredoxin peroxidases I and II with hydrogen peroxide and peroxynitrite: Rate constants by competitive kinetics. Free Radic. Biol. Med. 42:326‐334.
   Pak, J.H., Choi, W.H., Lee, H.M., Joo, W.D., Kim, J.H., Kim, Y.T., Kim, Y.M., and Nam, J.H. 2011. Peroxiredoxin 6 overexpression attenuates cisplatin‐induced apoptosis in human ovarian cancer cells. Cancer Invest. 29:21‐28.
   Parmigiani, R.B., Xu, W.S., Venta‐Perez, G., Erdjument‐Bromage, H., Yaneva, M., Tempst, P., and Marks, P.A. 2008. HDAC6 is a specific deacetylase of peroxiredoxins and is involved in redox regulation. Proc. Natl. Acad. Sci. U.S.A. 105:9633‐9638.
   Parsonage, D., Youngblood, D.S., Sarma, G.N., Wood, Z.A., Karplus, P.A., and Poole, L.B. 2005. Analysis of the link between enzymatic activity and oligomeric state in AhpC, a bacterial peroxiredoxin. Biochemistry 44:10583‐10592.
   Parsonage, D., Desrosiers, D.C., Hazlett, K.R., Sun, Y., Nelson, K.J., Cox, D.L., Radolf, J.D., and Poole, L.B. 2010a. Broad specificity AhpC‐like peroxiredoxin and its thioredoxin reductant in the sparse antioxidant defense system of Treponema pallidum. Proc. Natl. Acad. Sci. U.S.A. 107:6240‐6245.
   Parsonage, D., Reeves, S.A., Karplus, P.A., and Poole, L.B. 2010b. Engineering of fluorescent reporters into redox domains to monitor electron transfers. Methods Enzymol. 474:1‐21.
   Pascual, M.B., Mata‐Cabana, A., Florencio, F.J., Lindahl, M., and Cejudo, F.J. 2010. Overoxidation of 2‐Cys peroxiredoxin in prokaryotes: Cyanobacterial 2‐Cys peroxiredoxins sensitive to oxidative stress. J. Biol. Chem. 285:34485‐34492.
   Peskin, A.V., Low, F.M., Paton, L.N., Maghzal, G.J., Hampton, M.B., and Winterbourn, C.C. 2007. The high reactivity of peroxiredoxin 2 with H2O2 is not reflected in its reaction with other oxidants and thiol reagents. J. Biol. Chem. 282:11885‐11892.
   Phalen, T.J., Weirather, K., Deming, P.B., Anathy, V., Howe, A.K., van der Vliet, A., Jönsson, T.J., Poole, L.B., and Heintz, N.H. 2006. Oxidation state governs structural transitions in peroxiredoxin II that correlate with cell cycle arrest and recovery. J. Cell Biol. 175:779‐789.
   Poole, L.B. 2007. The catalytic mechanism of peroxiredoxins. In Peroxiredoxin Systems ( L. Flohé and J.R. Harris, eds.) pp. 61‐81. Springer, New York.
   Poole, L.B. and Claiborne, A. 1989. The non‐flavin redox center of the streptococcal NADH peroxidase. II. Evidence for a stabilized cysteine‐sulfenic acid. J. Biol. Chem. 264:12330‐12338.
   Poole, L.B. and Nelson, K.J. 2008. Discovering mechanisms of signaling‐mediated cysteine oxidation. Curr. Opin. Chem. Biol. 12:18‐24.
   Poole, L.B., Reynolds, C.M., Wood, Z.A., Karplus, P.A., Ellis, H.R., and Li Calzi, M. 2000. AhpF and other NADH: Peroxiredoxin oxidoreductases, homologues of low Mr thioredoxin reductase. Eur. J. Biochem. 267:6126‐6133.
   Poole, L.B., Karplus, P.A., and Claiborne, A. 2004. Protein sulfenic acids in redox signaling. Annu. Rev. Pharmacol. Toxicol. 44:325‐347.
   Quan, C., Cha, E.J., Lee, H.L., Han, K.H., Lee, K.M., and Kim, W.J. 2006. Enhanced expression of peroxiredoxin I and VI correlates with development, recurrence and progression of human bladder cancer. J. Urol. 175:1512‐1516.
   Rabilloud, T., Heller, M., Gasnier, F., Luche, S., Rey, C., Aebersold, R., Benahmed, M., Louisot, P., and Lunardi, J. 2002. Proteomics analysis of cellular response to oxidative stress. Evidence for in vivo overoxidation of peroxiredoxins at their active site. J. Biol. Chem. 277:19396‐19401.
   Rhee, S.G., Yang, K.S., Kang, S.W., Woo, H.A., and Chang, T.S. 2005. Controlled elimination of intracellular H(2)O(2): Regulation of peroxiredoxin, catalase, and glutathione peroxidase via post‐translational modification. Antioxid. Redox Signal. 7:619‐626.
   Roumes, H., Pires‐Alves, A., Gonthier‐Maurin, L., Dargelos, E., and Cottin, P. 2010. Investigation of peroxiredoxin IV as a calpain‐regulated pathway in cancer. Anticancer Res. 30:5085‐5089.
   Sarma, G.N., Nickel, C., Rahlfs, S., Fischer, M., Becker, K., and Karplus, P.A. 2005. Crystal structure of a novel Plasmodium falciparum 1‐Cys peroxiredoxin. J. Mol. Biol. 346:1021‐1034.
   Sayed, A.A. and Williams, D.L. 2004. Biochemical characterization of 2‐Cys peroxiredoxins from Schistosoma mansoni. J. Biol. Chem. 279:26159‐26166.
   Seo, M.S., Kang, S.W., Kim, K., Baines, I.C., Lee, T.H., and Rhee, S.G. 2000. Identification of a new type of mammalian peroxiredoxin that forms an intramolecular disulfide as a reaction intermediate. J. Biol. Chem. 275:20346‐20354.
   Seo, J.H., Koo, K.H., Kim, I.G., and Chae, H.Z. 2004. Ionizing radiation induced C‐terminal truncation of PrxII: A noble peroxidase activity enhancing mechanism. Free Radic. Biol. Med. 37:S15.
   Seo, J.H., Lim, J.C., Lee, D.Y., Kim, K.S., Piszczek, G., Nam, H.W., Kim, Y.S., Ahn, T., Yun, C.H., Kim, K., Chock, P.B., and Chae, H.Z. 2009. Novel protective mechanism against irreversible hyperoxidation of peroxiredoxin: Nalpha‐terminal acetylation of human peroxiredoxin II. J. Biol. Chem. 284:13455‐13465.
   Smith‐Pearson, P.S., Kooshki, M., Spitz, D.R., Poole, L.B., Zhao, W., and Robbins, M.E. 2008. Decreasing peroxiredoxin II expression decreases glutathione, alters cell cycle distribution, and sensitizes glioma cells to ionizing radiation and H(2)O(2). Free Radic. Biol. Med. 45:1178‐1189.
   Soito, L., Williamson, C., Knutson, S.T., Fetrow, J.S., Poole, L.B., and Nelson, K.J. 2011. PREX: PeroxiRedoxin classification indEX, a database of subfamily assignments across the diverse peroxiredoxin family. Nucleic Acids Res. 39:D332‐D337.
   Stacey, M.M., Peskin, A.V., Vissers, M.C., and Winterbourn, C.C. 2009. Chloramines and hypochlorous acid oxidize erythrocyte peroxiredoxin 2. Free Radic. Biol. Med. 47:1468‐1476.
   Stone, J.R. and Yang, S. 2006. Hydrogen peroxide: A signaling messenger. Antioxid. Redox Signal. 8:243‐270.
   Su, D., Berndt, C., Fomenko, D.E., Holmgren, A., and Gladyshev, V.N. 2007. A conserved cis‐proline precludes metal binding by the active site thiolates in members of the thioredoxin family of proteins. Biochemistry 46:6903‐6910.
   Szatrowski, T.P. and Nathan, C.F. 1991. Production of large amounts of hydrogen peroxide by human tumor cells. Cancer Res. 51:794‐798.
   Trujillo, M., Mauri, P., Benazzi, L., Comini, M., De Palma, A., Flohe, L., Radi, R., Stehr, M., Singh, M., Ursini, F., and Jaeger, T. 2006. The mycobacterial thioredoxin peroxidase can act as a one‐cysteine peroxiredoxin. J. Biol. Chem. 281:20555‐20566.
   Trujillo, M., Clippe, A., Manta, B., Ferrer‐Sueta, G., Smeets, A., Declercq, J.P., Knoops, B., and Radi, R. 2007. Pre‐steady state kinetic characterization of human peroxiredoxin 5: Taking advantage of Trp84 fluorescence increase upon oxidation. Arch. Biochem. Biophys. 467:95‐106.
   Veal, E.A., Day, A.M., and Morgan, B.A. 2007. Hydrogen peroxide sensing and signaling. Mol. Cell 26:1‐14.
   Wang, G., Olczak, A.A., Walton, J.P., and Maier, R.J. 2005. Contribution of the Helicobacter pylori thiol peroxidase bacterioferritin comigratory protein to oxidative stress resistance and host colonization. Infect. Immun. 73:378‐384.
   Wang, T., Tamae, D., LeBon, T., Shively, J.E., Yen, Y., and Li, J.J. 2005. The role of peroxiredoxin II in radiation‐resistant MCF‐7 breast cancer cells. Cancer Res. 65:10338‐10346.
   Winterbourn, C.C. 2008. Reconciling the chemistry and biology of reactive oxygen species. Nat. Chem. Biol. 4:278‐286.
   Woo, H.A., Yim, S.H., Shin, D.H., Kang, D., Yu, D.Y., and Rhee, S.G. 2010. Inactivation of peroxiredoxin I by phosphorylation allows localized H2O2 accumulation for cell signaling. Cell 140:517‐528.
   Wood, Z.A., Poole, L.B., Hantgan, R.R., and Karplus, P.A. 2002. Dimers to doughnuts: Redox‐sensitive oligomerization of 2‐cysteine peroxiredoxins. Biochemistry 41:5493‐5504.
   Wood, Z.A., Poole, L.B., and Karplus, P.A. 2003a. Peroxiredoxin evolution and the regulation of hydrogen peroxide signaling. Science 300:650‐653.
   Wood, Z.A., Schröder, E., Harris, J.R., and Poole, L.B. 2003b. Structure, mechanism and regulation of peroxiredoxins. Trends Biochem. Sci. 28:32‐40.
   Yamamoto, Y., Ritz, D., Planson, A.G., Jonsson, T.J., Faulkner, M.J., Boyd, D., Beckwith, J., and Poole, L.B. 2008. Mutant AhpC peroxiredoxins suppress thiol‐disulfide redox deficiencies and acquire deglutathionylating activity. Mol. Cell 29:36‐45.
   Yang, K.S., Kang, S.W., Woo, H.A., Hwang, S.C., Chae, H.Z., Kim, K., and Rhee, S.G. 2002. 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. 277:38029‐38036.
   Yeh, J.I., Claiborne, A., and Hol, W.G. 1996. Structure of the native cysteine‐sulfenic acid redox center of enterococcal NADH peroxidase refined at 2.8 Å resolution. Biochemistry 35:9951‐9957.
   Yuan, Y., Knaggs, M.H., Poole, L.B., Fetrow, J.S., and Salsbury, F.R. 2010. Conformational and oligomeric effects on the cysteine pK(a) of tryparedoxin peroxidase. J. Biomol. Struct. Dyn. 28:51‐70.
   Zhang, B., Wang, Y., and Su, Y. 2009. Peroxiredoxins, a novel target in cancer radiotherapy. Cancer Lett. 286:154‐160.
Key References
   Nelson et al., 2011. See above.
  A comprehensive bioinformatics analysis of the peroxiredoxin family of proteins, including subfamily assignments of >3500 peroxiredoxins and a discussion of the insights gained from this analysis.
   Hall et al., 2011. See above.
  An up‐to‐date review of what has been learned from the >70 peroxiredoxin structures in the Protein Data Bank.
   Flohé, 2010. See above.
  Provides a historical perspective of the emerging knowledge about oxidative stress defenses and thiol‐based regulation, including the properties and potential roles for peroxiredoxins in redox signaling.
Internet Resources
  PREX is a searchable database containing >6000 Prx protein sequences unambiguously classified into one of six distinct subclasses. Subfamily classifications use information around the active sites of structurally characterized subfamily members to search for sequences with conserved functionally relevant motifs (Nelson et al., ; Soito et al., ).
PDF or HTML at Wiley Online Library