Biochemistry (Moscow)

, Volume 77, Issue 10, pp 1097–1107 | Cite as

Recharging oxidative protein repair: Catalysis by methionine sulfoxide reductases towards their amino acid, protein, and model substrates

  • L. Tarrago
  • V. N. GladyshevEmail author


The sulfur-containing amino acid methionine (Met) in its free and amino acid residue forms can be readily oxidized to the R and S diastereomers of methionine sulfoxide (MetO). Methionine sulfoxide reductases A (MSRA) and B (MSRB) reduce MetO back to Met in a stereospecific manner, acting on the S and R forms, respectively. A third MSR type, fRMSR, reduces the R form of free MetO. MSRA and MSRB are spread across the three domains of life, whereas fRMSR is restricted to bacteria and unicellular eukaryotes. These enzymes protect against abiotic and biotic stresses and regulate lifespan. MSRs are thiol oxidoreductases containing catalytic redox-active cysteine or selenocysteine residues, which become oxidized by the substrate, requiring regeneration for the next catalytic cycle. These enzymes can be classified according to the number of redox-active cysteines (selenocysteines) and the strategies to regenerate their active forms by thioredoxin and glutaredoxin systems. For each MSR type, we review catalytic parameters for the reduction of free MetO, low molecular weight MetO-containing compounds, and oxidized proteins. Analysis of these data reinforces the concept that MSRAs reduce various types of MetO-containing substrates with similar efficiency, whereas MSRBs are specialized for the reduction of MetO in proteins.

Key words

enzyme catalysis methionine oxidation methionine sulfoxide methionine sulfoxide reductase sulfenic acid selenenic acid protein oxidation oxidative protein repair 


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  1. 1.
    Fukagawa, N. K. (2006) J. Nutr., 136, 1676S–1681S.PubMedGoogle Scholar
  2. 2.
    Luo, S., and Levine, R. L. (2009) FASEB J., 23, 464–472.PubMedCrossRefGoogle Scholar
  3. 3.
    Marino, S. M., and Gladyshev, V. N. (2010) J. Mol. Biol., 404, 902–916.PubMedCrossRefGoogle Scholar
  4. 4.
    Kochanczyk, M. (2011) BMC Struct. Biol., 11, 34.PubMedCrossRefGoogle Scholar
  5. 5.
    Rhee, S. G., and Woo, H. A. (2011) Antioxid. Redox. Signal., 15, 781–794.PubMedCrossRefGoogle Scholar
  6. 6.
    Tanner, J. J., Parsons, Z. D., Cummings, A. H., Zhou, H., and Gates, K. S. (2011) Antioxid. Redox Signal., 15, 77–97.PubMedCrossRefGoogle Scholar
  7. 7.
    Lee, B. C., and Gladyshev, V. N. (2011) Free Radic. Biol. Med., 50, 221–227.PubMedCrossRefGoogle Scholar
  8. 8.
    Brot, N., Weissbach, L., Werth, J., and Weissbach, H. (1981) Proc. Natl. Acad. Sci. USA, 78, 2155–2158.PubMedCrossRefGoogle Scholar
  9. 9.
    Grimaud, R., Ezraty, B., Mitchell, J. K., Lafitte, D., Briand, C., Derrick, P. J., and Barras, F. (2001) J. Biol. Chem., 276, 48915–48920.PubMedCrossRefGoogle Scholar
  10. 10.
    Kryukov, G. V., Kumar, R. A., Koc, A., Sun, Z., and Gladyshev, V. N. (2002) Proc. Natl. Acad. Sci. USA, 99, 4245–4250.PubMedCrossRefGoogle Scholar
  11. 11.
    Black, S., Harte, E. M., Hudson, B., and Wartofsky, L. (1960) J. Biol. Chem., 235, 2910–2916.Google Scholar
  12. 12.
    Ejiri, S. I., Weissbach, H., and Brot, N. (1979) J. Bacteriol., 139, 161–164.PubMedGoogle Scholar
  13. 13.
    Delaye, L., Becerra, A., Orgel, L., and Lazcano, A. (2007) J. Mol. Evol., 64, 15–32.PubMedCrossRefGoogle Scholar
  14. 14.
    Zhang, X-H., and Weissbach, H. (2008) Biol. Rev. Camb. Philos. Soc., 83, 249–257.PubMedCrossRefGoogle Scholar
  15. 15.
    Tarrago, L., Laugier, E., and Rey, P. (2009) Mol. Plant, 2, 202–217.PubMedCrossRefGoogle Scholar
  16. 16.
    Lin, Z., Johnson, L. C., Weissbach, H., Brot, N., Lively, M. O., and Lowther, W. T. (2007) Proc. Natl. Acad. Sci. USA, 104, 9597–9602.PubMedCrossRefGoogle Scholar
  17. 17.
    Le, D. T., Lee, B. C., Marino, S. M., Zhang, Y., Fomenko, D. E., Kaya, A., Hacioglu, E., Kwak, G. H., Koc, A., Kim, H. Y., and Gladyshev, V. N. (2009) J. Biol. Chem., 284, 4354–4364.PubMedCrossRefGoogle Scholar
  18. 18.
    Ezraty, B., Bos, J., Barras, F., and Aussel, L. (2005) J. Bacteriol., 187, 231–237.PubMedCrossRefGoogle Scholar
  19. 19.
    St John, G., Brot, N., Ruan, J., Erdjument-Bromage, H., Tempst, P., Weissbach, H., and Nathan, C. (2001) Proc. Natl. Acad. Sci. USA, 98, 9901–9906.PubMedCrossRefGoogle Scholar
  20. 20.
    Alamuri, P., and Maier, R. J. (2004) Mol. Microbiol., 53, 1397–1406.PubMedCrossRefGoogle Scholar
  21. 21.
    Lee, W. L., Gold, B., Darby, C., Brot, N., Jiang, X., de Carvalho, L. P., Wellner, D., St John, G., Jacobs, W. R., Jr., and Nathan, C. (2009) Mol. Microbiol., 71, 583–593.PubMedCrossRefGoogle Scholar
  22. 22.
    Koc, A., Gasch, A. P., Rutherford, J. C., Kim, H-Y., and Gladyshev, V. N. (2004) Proc. Natl. Acad. Sci. USA, 101, 7999–8004.PubMedCrossRefGoogle Scholar
  23. 23.
    Kaya, A., Koc, A., Lee, B. C., Fomenko, D. E., Rederstorff, M., Krol, A., Lescure, A., and Gladyshev, V. N. (2010) Biochemistry, 49, 8618–8625.PubMedCrossRefGoogle Scholar
  24. 24.
    Minniti, A. N., Cataldo, R., Trigo, C., Vasquez, L., Mujica, P., Leighton, F., Inestrosa, N. C., and Aldunate, R. (2009) Aging Cell, 8, 690–705.PubMedCrossRefGoogle Scholar
  25. 25.
    Zhang, C., Jia, P., Jia, Y., Weissbach, H., Webster, K. A., Huang, X., Lemanski, S. L., Achary, M., and Lemanski, L. F. (2010) J. Cell Biochem., 111, 94–103.PubMedCrossRefGoogle Scholar
  26. 26.
    Romero, H. M., Berlett, B. S., Jensen, P. J., Pell, E. J., and Tien, M. (2004) Plant Physiol., 136, 3784–3794.PubMedCrossRefGoogle Scholar
  27. 27.
    Guo, X., Wu, Y., Wang, Y., Chen, Y., and Chu, C. (2009) Planta, 230, 227–238.PubMedCrossRefGoogle Scholar
  28. 28.
    Ruan, H., Tang, X. D., Chen, M. L., Joiner, M. L., Sun, G., Brot, N., Weissbach, H., Heinemann, S. H., Iverson, L., Wu, C. F., and Hoshi, T. (2002) Proc. Natl. Acad. Sci. USA, 99, 2748–2753.PubMedCrossRefGoogle Scholar
  29. 29.
    Picot, C. R., Petropoulos, I., Perichon, M., Moreau, M., Nizard, C., and Friguet, B. (2005) Free Radic. Biol. Med., 39, 1332–1341.PubMedCrossRefGoogle Scholar
  30. 30.
    Haenold, R., Wassef, R., Brot, N., Neugebauer, S., Leipold, E., Heinemann, S. H., and Hoshi, T. (2008) Free Radic. Res., 42, 978–988.PubMedCrossRefGoogle Scholar
  31. 31.
    Kwon, S. J., Kwon, S. I., Bae, M. S., Cho, E. J., and Park, O. K. (2007) Plant Cell. Physiol., 48, 1713–1723.PubMedCrossRefGoogle Scholar
  32. 32.
    Laugier, E., Tarrago, L., Vieira Dos Santos, C., Eymery, F., Havaux, M., and Rey, P. (2010) Plant J., 61, 271–282.PubMedCrossRefGoogle Scholar
  33. 33.
    Cabreiro, F., Picot, C. R., Friguet, B., and Petropoulos, I. (2006) Ann. N. Y. Acad. Sci., 1067, 37–44.PubMedCrossRefGoogle Scholar
  34. 34.
    Koc, A., and Gladyshev, V. N. (2007) Ann. N. Y. Acad. Sci., 1100, 383–386.PubMedCrossRefGoogle Scholar
  35. 35.
    Shchedrina, V. A., Vorbruggen, G., Lee, B. C., Kim, H. Y., Kabil, H., Harshman, L. G., and Gladyshev, V. N. (2009) Mech. Ageing Dev., 130, 429–443.PubMedCrossRefGoogle Scholar
  36. 36.
    Achilli, C., Ciana, A., Rossi, A., Balduini, C., and Minetti, G. (2008) J. Leukoc. Biol., 83, 181–189.PubMedCrossRefGoogle Scholar
  37. 37.
    Rosen, H., Klebanoff, S. J., Wang, Y., Brot, N., Heinecke, J. W., and Fu, X. (2009) Proc. Natl. Acad. Sci. USA, 106, 18686–18691.PubMedCrossRefGoogle Scholar
  38. 38.
    Mahawar, M., Tran, V., Sharp, J. S., and Maier, R. J. (2011) J. Biol. Chem., 286, 19159–19169.PubMedCrossRefGoogle Scholar
  39. 39.
    Lowther, W. T., Weissbach, H., Etienne, F., Brot, N., and Matthews, B. W. (2002) Nat. Struct. Biol., 9, 348–352.PubMedGoogle Scholar
  40. 40.
    Kim, H-Y., Fomenko, D. E., Yoon, Y-E., and Gladyshev, V. N. (2006) Biochemistry, 45, 13697–13704.PubMedCrossRefGoogle Scholar
  41. 41.
    Boschi-Muller, S., Azza, S., Sanglier-Cianferani, S., Talfournier, F., Van Dorsselear, A., and Branlant, G. (2000) J. Biol. Chem., 275, 35908–35913.PubMedCrossRefGoogle Scholar
  42. 42.
    Antoine, M., Gand, A., Boschi-Muller, S., and Branlant, G. (2006) J. Biol. Chem., 281, 39062–39070.PubMedCrossRefGoogle Scholar
  43. 43.
    Boschi-Muller, S., Gand, A., and Branlant, G. (2008) Arch. Biochem. Biophys., 474, 266–273.PubMedCrossRefGoogle Scholar
  44. 44.
    Lowther, W. T., Brot, N., Weissbach, H., and Matthews, B. W. (2000) Biochemistry, 39, 13307–13312.PubMedCrossRefGoogle Scholar
  45. 45.
    Tete-Favier, F., Cobessi, D., Boschi-Muller, S., Azza, S., Branlant, G., and Aubry, A. (2000) Structure, 8, 1167–1178.PubMedCrossRefGoogle Scholar
  46. 46.
    Taylor, A. B., Benglis, D. M., Jr., Dhandayuthapani, S., and Hart, P. J. (2003) J. Bacteriol., 185, 4119–4126.PubMedCrossRefGoogle Scholar
  47. 47.
    Rouhier, N., Kauffmann, B., Tete-Favier, F., Palladino, P., Gans, P., Branlant, G., Jacquot, J. P., and Boschi-Muller, S. (2007) J. Biol. Chem., 282, 3367–3378.PubMedCrossRefGoogle Scholar
  48. 48.
    Ranaivoson, F. M., Antoine, M., Kauffmann, B., Boschi-Muller, S., Aubry, A., Branlant, G., and Favier, F. (2008) J. Mol. Biol., 377, 268–280.PubMedCrossRefGoogle Scholar
  49. 49.
    Lim, J. C., You, Z., Kim, G., and Levine, R. L. (2011) Proc. Natl. Acad. Sci. USA, 108, 10472–10477.PubMedCrossRefGoogle Scholar
  50. 50.
    Kim, H-Y., and Gladyshev, V. N. (2005) PLoS Biol., 3, e375.PubMedCrossRefGoogle Scholar
  51. 51.
    Robinet, J. J., Dokainish, H. M., Paterson, D. J., and Gauld, J. W. (2011) J. Phys. Chem. B, 115, 9202–9212.PubMedCrossRefGoogle Scholar
  52. 52.
    Neiers, F., Sonkaria, S., Olry, A., Boschi-Muller, S., and Branlant, G. (2007) J. Biol. Chem., 282, 32397–32405.PubMedCrossRefGoogle Scholar
  53. 53.
    Neiers, F., Boschi-Muller, S., and Branlant, G. (2011) J. Phys. Chem. B, 115, 10775; 10776–10777.CrossRefGoogle Scholar
  54. 54.
    Carella, M., Becher, J., Ohlenschlager, O., Ramachandran, R., Guhrs, K. H., Wellenreuther, G., Meyer-Klaucke, W., Heinemann, S. H., and Gorlach, M. (2011) Mol. Microbiol., 79, 342–358.PubMedCrossRefGoogle Scholar
  55. 55.
    Tarrago, L., Laugier, E., Zaffagnini, M., Marchand, C., Le Marechal, P., Rouhier, N., Lemaire, S. D., and Rey, P. (2009) J. Biol. Chem., 284, 18963–18971.PubMedCrossRefGoogle Scholar
  56. 56.
    Tarrago, L., Laugier, E., Zaffagnini, M., Marchand, C. H., Le Marechal, P., Lemaire, S. D., and Rey, P. (2010) J. Biol. Chem., 285, 14964–14972.PubMedCrossRefGoogle Scholar
  57. 57.
    Kumar, R. A., Koc, A., Cerny, R. L., and Gladyshev, V. N. (2002) J. Biol. Chem., 277, 37527–37535.PubMedCrossRefGoogle Scholar
  58. 58.
    Ma, X. X., Guo, P. C., Shi, W. W., Luo, M., Tan, X. F., Chen, Y., and Zhou, C. Z. (2011) J. Biol. Chem., 286, 13430–13437.PubMedCrossRefGoogle Scholar
  59. 59.
    Tarrago, L., Kaya, A., Weerapana, E., Marino, S. M., and Gladyshev, V. N. (2012) J. Biol. Chem., 287, 24448–24459.PubMedCrossRefGoogle Scholar
  60. 60.
    Olry, A., Boschi-Muller, S., and Branlant, G. (2004) Biochemistry, 43, 11616–11622.PubMedCrossRefGoogle Scholar
  61. 61.
    Gladyshev, V. N. (2002) Proteins, 46, 149–152.PubMedCrossRefGoogle Scholar
  62. 62.
    Boschi-Muller, S., Azza, S., and Branlant, G. (2001) Protein Sci., 10, 2272–2279.PubMedCrossRefGoogle Scholar
  63. 63.
    Kim, H-Y. (2012) Acta Biochim. Biophys. Sin., 44, 623–627.PubMedCrossRefGoogle Scholar
  64. 64.
    Flohe, L., Toppo, S., Cozza, G., and Ursini, F. (2011) Antioxid. Redox Signal., 15, 763–780.PubMedCrossRefGoogle Scholar
  65. 65.
    Boschi-Muller, S., Olry, A., Antoine, M., and Branlant, G. (2005) Biochim. Biophys. Acta, 1703, 231–238.PubMedCrossRefGoogle Scholar
  66. 66.
    Neiers, F., Kriznik, A., Boschi-Muller, S., and Branlant, G. (2004) J. Biol. Chem., 279, 42462–42468.PubMedCrossRefGoogle Scholar
  67. 67.
    Chibani, K., Tarrago, L., Gualberto, J. M., Wingsle, G., Rey, P., Jacquot, J. P., and Rouhier, N. (2012) Plant Physiol., 159, 592–605.PubMedCrossRefGoogle Scholar
  68. 68.
    Ding, D., Sagher, D., Laugier, E., Rey, P., Weissbach, H., and Zhang, X. H. (2007) Biochem. Biophys. Res. Commun., 361, 629–633.PubMedCrossRefGoogle Scholar
  69. 69.
    Kim, H-Y., and Kim, J-R. (2008) Biochem. Biophys. Res. Commun., 371, 490–494.PubMedCrossRefGoogle Scholar
  70. 70.
    Bong, S. M., Kwak, G. H., Moon, J. H., Lee, K. S., Kim, H. S., Kim, H. Y., and Chi, Y. M. (2010) J. Biol. Chem., 285, 25044–25052.PubMedCrossRefGoogle Scholar
  71. 71.
    Gruez, A., Libiad, M., Boschi-Muller, S., and Branlant, G. (2010) J. Biol. Chem., 285, 25033–25043.PubMedCrossRefGoogle Scholar
  72. 72.
    Ritz, D., and Beckwith, J. (2001) Annu. Rev. Microbiol., 55, 21–48.PubMedCrossRefGoogle Scholar
  73. 73.
    Jacob, C., Kriznik, A., Boschi-Muller, S., and Branlant, G. (2011) FEBS Lett., 585, 1905–1909.PubMedCrossRefGoogle Scholar
  74. 74.
    Mouaheb, N., Thomas, D., Verdoucq, L., Monfort, P., and Meyer, Y. (1998) Proc. Natl. Acad. Sci. USA, 95, 3312–3317.PubMedCrossRefGoogle Scholar
  75. 75.
    Lemaire, S. D., Guillon, B., Le Marechal, P., Keryer, E., Miginiac-Maslow, M., and Decottignies, P. (2004) Proc. Natl. Acad. Sci. USA, 101, 7475–7480.PubMedCrossRefGoogle Scholar
  76. 76.
    Motohashi, K., Kondoh, A., Stumpp, M. T., and Hisabori, T. (2001) Proc. Natl. Acad. Sci. USA, 98, 11224–11229.PubMedCrossRefGoogle Scholar
  77. 77.
    Rey, P., Cuine, S., Eymery, F., Garin, J., Court, M., Jacquot, J. P., Rouhier, N., and Broin, M. (2005) Plant J., 41, 31–42.PubMedCrossRefGoogle Scholar
  78. 78.
    Montrichard, F., Alkhalfioui, F., Yano, H., Vensel, W. H., Hurkman, W. J., and Buchanan, B. B. (2009) J. Prot., 72, 452–474.CrossRefGoogle Scholar
  79. 79.
    Ezraty, B., Aussel, L., and Barras, F. (2005) Biochim. Biophys. Acta, 1703, 221–229.PubMedCrossRefGoogle Scholar
  80. 80.
    Vieira Dos Santos, C., Laugier, E., Tarrago, L., Massot, V., Issakidis-Bourguet, E., Rouhier, N., and Rey, P. (2007) FEBS Lett., 581, 4371–4376.PubMedCrossRefGoogle Scholar
  81. 81.
    Stewart, E. J., Aslund, F., and Beckwith, J. (1998) EMBO J., 17, 5543–5550.PubMedCrossRefGoogle Scholar
  82. 82.
    Ezraty, B., Grimaud, R., El Hassouni, M., Moinier, D., and Barras, F. (2004) EMBO J., 23, 1868–1877.PubMedCrossRefGoogle Scholar
  83. 83.
    Vieira Dos Santos, C., Cuine, S., Rouhier, N., and Rey, P. (2005) Plant Physiol., 138, 909–922.PubMedCrossRefGoogle Scholar
  84. 84.
    Olry, A., Boschi-Muller, S., Marraud, M., Sanglier-Cianferani, S., Van Dorsselear, A., and Branlant, G. (2002) J. Biol. Chem., 277, 12016–12022.PubMedCrossRefGoogle Scholar
  85. 85.
    Chibani, K., Tarrago, L., Schurmann, P., Jacquot, J.-P., and Rouhier, N. (2011) FEBS Lett., 585, 1077–1081.PubMedCrossRefGoogle Scholar
  86. 86.
    Couturier, J., Stroher, E., Albetel, A. N., Roret, T., Muthuramalingam, M., Tarrago, L., Seidel, T., Tsan, P., Jacquot, J. P., Johnson, M. K., Dietz, K. J., Didierjean, C., and Rouhier, N. (2011) J. Biol. Chem., 286, 27515–27527.PubMedCrossRefGoogle Scholar
  87. 87.
    Trujillo, M., Ferrer-Sueta, G., Thomson, L., Flohe, L., and Radi, R. (2007) Subcell. Biochem., 44, 83–113.PubMedCrossRefGoogle Scholar
  88. 88.
    Xiong, Y., Chen, B., Smallwood, H. S., Urbauer, R. J., Markille, L. M., Galeva, N., Williams, T. D., and Squier, T. C. (2006) Biochemistry, 45, 14642–14654.PubMedCrossRefGoogle Scholar
  89. 89.
    Tarrago, L., Kieffer-Jaquinod, S., Lamant, T., Marcellin, M. N., Garin, J. R., Rouhier, N., and Rey, P. (2012) Antioxid. Redox Signal., 16, 79–84.PubMedCrossRefGoogle Scholar
  90. 90.
    Lee, B. C., Fomenko, D. E., and Gladyshev, V. N. (2011) ACS Chem. Biol., 6, 1029–1035.PubMedCrossRefGoogle Scholar
  91. 91.
    Lee, B. C., Le, D. T., and Gladyshev, V. N. (2008) J. Biol. Chem., 283, 28361–28369.PubMedCrossRefGoogle Scholar
  92. 92.
    Ranaivoson, F. M., Neiers, F., Kauffmann, B., Boschi-Muller, S., Branlant, G., and Favier, F. (2009) J. Mol. Biol., 394, 83–93.PubMedCrossRefGoogle Scholar
  93. 93.
    Aachmann, F. L., Kwak, G. H., Del Conte, R., Kim, H. Y., Gladyshev, V. N., and Dikiy, A. (2011) Proteins, 79, 3123–3131.PubMedCrossRefGoogle Scholar
  94. 94.
    Aachmann, F. L., Sal, L. S., Kim, H. Y., Marino, S. M., Gladyshev, V. N., and Dikiy, A. (2010) J. Biol. Chem., 285, 33315–33323.PubMedCrossRefGoogle Scholar
  95. 95.
    Ghesquiere, B., Jonckheere, V., Colaert, N., Van Durme, J., Timmerman, E., Goethals, M., Schymkowitz, J., Rousseau, F., Vandekerckhove, J., and Gevaert, K. (2011) Mol. Cell. Proteomics, 10, M110.006866.PubMedCrossRefGoogle Scholar
  96. 96.
    Kim, G., Cole, N. B., Lim, J. C., Zhao, H., and Levine, R. L. (2010) J. Biol. Chem., 285, 18085–18094.PubMedCrossRefGoogle Scholar
  97. 97.
    Lim, J. C., Gruschus, J. M., Ghesquiere, B., Kim, G., Piszczek, G., Tjandra, N., and Levine, R. L. (2012) J. Biol. Chem., 287, 25589–25595.PubMedCrossRefGoogle Scholar

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© Pleiades Publishing, Ltd. 2012

Authors and Affiliations

  1. 1.Brigham and Women’s Hospital and Harvard Medical SchoolBostonUSA

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