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Functional Role of Methionine Oxidation in Proteins: Arguments for and against

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Abstract—

The conversion of methionine to methionine sulfoxide (MetO) is one of the most common oxidative modifications in proteins due to the special susceptibility of methionine to oxidative conditions. Methionine oxidation can affect the protein structure and function, while the level of MetO increases with the development of oxidative stress. Most cells contain methionine sulfoxide reductases (MSRs), which catalyze a thioredoxin-dependent reduction of methionine sulfoxide to the original methionine. It was demonstrated that mutations leading to a decrease in MSR activity are associated with a decrease in the resistance of some cells to oxidative stress, while mutations leading to an overproduction of MSR activity result in an increase in resistance to oxidative stress. The redox reactions of methionines in the functional regulation of some intracellular proteins, actin, and calmodulin, are analyzed in the work, and the presence of antioxidant methionines in intracellular proteins, such as glutamine synthetase, 15-lipoxygenase, recombinant proteins, interferon α-2b, tissue plasminogen activator, and human stem cell factor, is discussed. The absence of MSR in the blood plasma makes the oxidation of methionines in the proteins irreversible; therefore, the ability of methionines to serve as interceptors of oxidant molecules without impairment of the function of plasma proteins is quite controversial. Antioxidant methionines were found in a number of proteins, such as macroglobulin, antithrombin III, and blood coagulation factor XIII. However, no antioxidant methionines were detected for most blood plasma proteins. There is a correlation between the oxidation of methionines and the development of pathological conditions in the organism.

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REFERENCES

  1. Aledo, J.C., Methionine in proteins: the Cinderella of the proteinogenic amino acids, Protein Sci., 2019, vol. 28, pp. 1785–1796.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Aledo, J.C., Li, Y., de Magalhães, J.P., et al., Mitochondrially encoded methionine is inversely related to longevity in mammals, Aging Cell, 2011, vol. 10, pp. 198–207.

    Article  CAS  PubMed  Google Scholar 

  3. Aledo, J.C., Valverde, H., and De Magalhães, J.P., Mutational bias plays an important role in shaping longevity-related amino acid content in mammalian mtDNA-encoded proteins, J. Mol. Evol., 2012, vol. 74, pp. 332–341.

    Article  CAS  PubMed  Google Scholar 

  4. Aledo, J.C., Cantón, F.R., and Veredas, F.J., Sulphur atoms from methionines interacting with aromatic residues are less prone to oxidation, Sci. Rep., 2015, vol. 5, p. 16955.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bagoly, Z. and Muszbek, L., Factor XIII: what does it look like? J. Thromb. Haemostasis, 2019, vol. 17, pp. 714–716.

    Article  Google Scholar 

  6. Barbato, G., Ikura, M., Kay, L.E., et al., Backbone dynamics of calmodulin studied by 15N relaxation using inverse detected two-dimensional NMR spectroscopy: the central helix is flexible, Biochemistry, 1992, vol. 31, vol. 5269–5278.

    Google Scholar 

  7. Bender, A., Hajieva, P., and Moosmann, B., Adaptive antioxidant methionine accumulation in respiratory chain complexes explains the use of a deviant genetic code in mitochondria, Proc. Natl. Acad. Sci. U.S.A., 2008, vol. 105, pp. 16496–16501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Bruschi, M., Candiano, G., Santucci, L., and Ghiggeri, G.M., Oxidized albumin. The long way of a protein of uncertain function, Biochim. Biophys. Acta, Gen. Subj., 2013, vol. 1830, pp. 5473–5479.

    Article  CAS  Google Scholar 

  9. Burney, P.R., White, N., and Pfaendtner, J., Structural effects of methionine oxidation on isolated subdomains of human fibrin D and αC regions, PLoS One, 2014, vol. 9, pp. 1–10.

    Article  Google Scholar 

  10. Carocho, M. and Ferreira, I.C., A review on antioxidants, prooxidants and related controversy: natural and synthetic compounds, screening and analysis methodologies and future perspectives, Food Chem. Toxicol., 2013, vol. 51, pp. 15–25.

    Article  CAS  PubMed  Google Scholar 

  11. Carrell, N.A., Erickson, H.P., and McDonagh, J., Electron microscopy and hydrodynamic properties of factor XIII subunits, J. Biol. Chem., 1989, vol. 264, pp. 551–556.

    Article  CAS  PubMed  Google Scholar 

  12. Carrell, R.W., Stein, P.E., Fermi, G., and Wardell, M.R., Biological implications of a 3 Å structure of dimeric antithrombin, Structure, 1994, vol. 2, pp. 257–270.

    Article  CAS  PubMed  Google Scholar 

  13. Cater, J.H., Wilson, M.R., and Wyatt, A.R., Alpha-2-macroglobulin, a hypochlorite-regulated chaperone and immune system modulator, Oxid. Med. Cell. Longevity, 2019, vol. 2019, art. ID 5410657.

    Article  Google Scholar 

  14. Chao, C.C., Ma, Y.S., and Stadtman, E.R., Modification of protein surface hydrophobicity and methionine oxidation by oxidative systems, Proc. Natl. Acad. Sci. U.S.A., 1997, vol. 94, pp. 2969–2974.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Chen, B., Mayer, M.U., and Squier, T.C., Structural uncoupling between opposing domains of oxidized calmodulin underlies the enhanced binding affinity and inhibition of the plasma membrane Ca-ATPase, Biochemistry, 2005, vol. 44, pp. 4737–4747.

    Article  CAS  PubMed  Google Scholar 

  16. Chin, D. and Means, A.R., Calmodulin: a prototypical calcium sensor, Trends Cell Biol., 2000, vol. 10, pp. 322–328.

    Article  CAS  PubMed  Google Scholar 

  17. Chyan, C.-L., Irene, D., and Lin, S.-M., The recognition of calmodulin to the target sequence of calcineurin—a novel binding mode, Molecules, 2017, vol. 22, p. 1584.

    Article  PubMed Central  Google Scholar 

  18. Cobley, J.N. Mechanisms of mitochondrial ROS production in assisted reproduction: the known, the unknown, and the intriguing, Antioxidants (Basel), 2020, vol. 9, p. 933.

    Article  CAS  PubMed Central  Google Scholar 

  19. Dahl, J.U., Gray, M.J., and Jakob, U., Protein quality control under oxidative stress conditions, J. Mol. Biol., 2015, vol. 427, pp. 1549–1563.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Davies, M.J., Protein oxidation and peroxidation, Biochem. J., 2016, vol. 473, pp. 805–825.

    Article  CAS  PubMed  Google Scholar 

  21. De Cristofaro, R. and Landolfi, R., Oxidation of human alpha-thrombin by the myeloperoxidase-H2O2-chloride system: structural and functional effects, Thromb. Haemostasis, 2000, vol. 83, pp. 253–261.

    Article  CAS  Google Scholar 

  22. De Vries, J.J., Snoek, C.J.M., Rijken, D.C., and de Maat, M.P.M., Effects of post-translational modifications of fibrinogen on clot formation, clot structure, and fibrinolysis, Arterioscler., Thromb. Vasc. Biol., 2020, vol. 40, pp. 554–569.

    Article  CAS  Google Scholar 

  23. Douglas, T., Daniel, D.S., Parida, B.K., et al., Methionine sulfoxide reductase A (MsrA) deficiency affects the survival of Mycobacterium smegmatis within macrophages, J. Bacteriol., 2004, vol. 186, pp. 3590–3598.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Drazic, A. and Winter, J., The physiological role of reversible methionine oxidation, Biochim. Biophys. Acta, Proteins Proteomics, 2014, vol. 1844, pp. 1367–1382.

    Article  CAS  Google Scholar 

  25. Elmallah, M.I., Borgmeyer, U., Betzel, C., and Redecke, L., Impact of methionine oxidation as an initial event on the pathway of human prion protein conversion, Prion, 2013, vol. 7, pp. 404–411.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Gan, Q.F., Witkop, G.L., Sloane, D.L., et al., Identification of a specific methionine in mammalian 15-lipoxygenase which is oxygenated by the enzyme product 13-HPODE: dissociation of sulfoxide formation from self-inactivation, Biochemistry, 1995, vol. 34, pp. 7069–7079.

    Article  CAS  PubMed  Google Scholar 

  27. Garner, B., Waldeck, A.R., Witting, P.K., et al., Oxidation of high density lipoproteins. II. Evidence for direct reduction of lipid hydroperoxides by methionine residues of apolipoproteins AI and AII, J. Biol. Chem., 1998, vol. 273, pp. 6088–6095.

    Article  CAS  PubMed  Google Scholar 

  28. Gellman, S.H., On the role of methionine residues in the sequence independent recognition of nonpolar protein surfaces, Biochemistry, 1991, vol. 30, pp. 6633–6636.

    Article  CAS  PubMed  Google Scholar 

  29. Gifford, J.L., Walsh, M.P., and Vogel, H.J., Structures and metal-ion-binding properties of the Ca2+-binding helix-loop-helix EF-hand motifs, Biochem. J., 2007, vol. 405, pp. 199–221.

    Article  CAS  PubMed  Google Scholar 

  30. Gray, E. and Barrowcliffe, T.W., Inhibition of antithrombin III by lipid peroxides, Thromb. Res., 1985, vol. 37, pp. 241–250.

    Article  CAS  PubMed  Google Scholar 

  31. Griffiths, H.R., Dias, I.H., Willetts, R.S., and Devitt, A., Redox regulation of protein damage, Redox Biol., 2014, vol. 2, pp. 430–435.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Grintsevich, E.E., Ge, P., Sawaya, M.R., et al., Catastrophic disassembly of actin filaments via Mical-mediated oxidation, Nat. Commun., 2017, vol. 8, p. 2183.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Grintsevich, E.E., Yesilyurt, H.G., Rich, S.K., et al., F-actin dismantling through a redox-driven synergy between Mical and cofilin, Nat. Cell. Biol., 2016, vol. 18, vol. 876–885.

    Book  Google Scholar 

  34. Grivennikova, V.G. and Vinogradov, A.D., Generation of reactive oxygen species by mitochondria, Usp. Biol. Khim., 2013, vol. 53, pp. 245–296.

    Google Scholar 

  35. Grune, T., Reinheckel, T., and Davies, K.J., Degradation of oxidized proteins in K562 human hematopoietic cells by proteasome, J. Biol. Chem., 1996, vol. 271, pp. 15504–15509.

    Article  CAS  PubMed  Google Scholar 

  36. Grune, T., Catalgol, B., and Jung, T., Protein Oxidation and Aging, Chichester: Wiley, 2013.

    Google Scholar 

  37. Gu, S.X., Stevens, J.W., and Lentz, S.R., Regulation of thrombosis and vascular function by protein methionine oxidation, Blood, 2015, vol. 125, pp. 3851–3859.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Gutmann, C., Siow, R., Gwozdz, A.M., et al., Reactive oxygen species in venous thrombosis, Int. J. Mol. Sci., 2020, vol. 21, p. 1918.

    Article  CAS  PubMed Central  Google Scholar 

  39. Hawkins, C.L., Pattison, D.I., and Davies, M.J., Hypochlorite-induced oxidation of amino acids, peptides and proteins, Amino Acids, 2003, vol. 25, pp. 259–274.

    Article  CAS  PubMed  Google Scholar 

  40. Hsu, Y.R., Narhi, L.O., and Spahr, C., In vitro methionine oxidation of Escherichia coli-derived human stem cell factor: effects on the molecular structure, biological activity, and dimerization, Protein Sci., 1996, vol. 5, pp. 1165–1173.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Hung, R.-J., Park, C.W., and Terman, J.R., Direct redox regulation of F-actin assembly and disassembly by Mical, Science, 2011, vol. 334, pp. 1710–1714.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Hung, R.-J., Spaeth, C.S., Yesilyurt, H.G., and Terman, J.R., SelR reverses Mical-mediated oxidation of actin to regulate F-actin dynamics, Nat. Cell. Biol., 2013, vol. 15, pp. 1445–1454.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Karbyshev, M.S. and Abdullaev, Sh.P., Biokhimiya oksidativnogo stressa. Okislitel’nyi stress. Prooksidanty i antioksidanty (Biochemistry of Oxidative Stress. Oxidative Stress. Prooxidants and Antioxidants), Moscow, 2018.

  44. Kattula, S., Byrnes, J.R., and Wolberg, A.S., Fibrinogen and fibrin in hemostasis and thrombosis, Arterioscler., Thromb., Vasc. Biol., 2017, vol. 37, p. e13–e21.

    Article  CAS  Google Scholar 

  45. Keck, R.G., The use of t-butyl hydroperoxide as a probe for methionine oxidation in proteins, Anal. Biochem., 1996, vol. 236, pp. 56–62.

    Article  CAS  PubMed  Google Scholar 

  46. Khan, S.A. and Khan, F.H., Hydroxyl radical mediates oxidative modification of caprine alpha-2-macroglobulin, Protein Pept. Lett., 2009, vol. 16, pp. 32–35.

    Article  CAS  PubMed  Google Scholar 

  47. Lankin, V.Z., Tikhaze, A.K., and Belenkov, Yu.N., Svobodnoradikal’nye protsessy v norme i pri patologicheskikh sostoyaniyakh (posobie dlya vrachei) (Free Radical Processes in Normal and Pathological Conditions: Manual for Physicians), Moscow: Nats. Med. Issled. Tsentr Kardiol., Minist. Zdravookhr. RF, 2001.

  48. Le-Donne, I., Rossi, R., Milzani, A., et al., The actin cytoskeleton response to oxidants: from small heat shock protein phosphorylation to changes in the redox state of actin itself, Free Radical Biol. Med., 2001, vol. 31, pp. 1624–1632.

    Article  Google Scholar 

  49. Lim, J.C., You, Z., Kim, G., and Levine, R.L., Methionine sulfoxide reductase A is a stereospecific methionine oxidase, Proc. Natl. Acad. Sci. U.S.A., 2011, vol. 108, pp. 10472–10477.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Lim, J.C., Kim, G., and Levine, R.L., Stereospecific oxidation of calmodulin by methionine sulfoxide reductase A, Free Radical Biol. Med., 2013, vol. 61, pp. 257–264.

    Article  CAS  Google Scholar 

  51. Lim, J., Kim, G., and Levine, R., Methionine in proteins: it’s not just for protein initiation anymore, Neurochem. Res., 2019, vol. 44, pp. 1–11.

    Article  Google Scholar 

  52. Lishko, V.K., Podolnikova, N.P., Yakubenko, V.P., et al., Multiple binding sites in fibrinogen for integrin αMβ2 (Mac-1), J. Biol. Chem., 2004, vol. 279, pp. 44897–44906.

    Article  CAS  PubMed  Google Scholar 

  53. Liu, F., Chu, X., Lu, H.P., and Wang, J., Molecular mechanism of multispecific recognition of calmodulin through conformational changes, Proc. Natl. Acad. Sci. U.S.A., 2017, vol. 114, pp. E3927–E3934.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Lu, A.L., Li, X., Gu, Y., et al., Repair of oxidative DNA damage: mechanisms and functions, Cell. Biochem. Biophys., 2001, vol. 35, pp. 141–170.

    Article  CAS  PubMed  Google Scholar 

  55. Manta, B. and Gladyshev, V.N., Regulated methionine oxidation by monooxygenases, Free Radical Biol. Med., 2017, vol. 109, pp. 141–155.

    Article  CAS  Google Scholar 

  56. Marimoutou, M., Springer, D.A., Liu, C., et al., Oxidation of methionine 77 in calmodulin alters mouse growth and behavior, Antioxidants (Basel), 2018, vol. 7, no. 10, p. 140.

    Article  PubMed Central  Google Scholar 

  57. Marrero, A., Duquerroy, S., Trapani, S., et al., The crystal structure of human α2-macroglobulin reveals a unique molecular cage, Angew. Chem., 2012, vol. 51, pp. 3340–3344.

    Article  CAS  Google Scholar 

  58. Martinez, M., Weisel, J.W., and Ischiropoulos, H., Functional impact of oxidative posttranslational modifications on fibrinogen and fibrin clots, Free Radical Biol. Med., 2013, vol. 65, pp. 411–418.

    Article  CAS  Google Scholar 

  59. McCarthy, M.R., Thompson, A.R., Nitu, F., et al., Impact of methionine oxidation on calmodulin structural dynamics, Biochem. Biophys. Res. Commun., 2015, vol. 456, pp. 567–572.

    Article  CAS  PubMed  Google Scholar 

  60. Men’shchikova, E.B., Lankin, V.Z., Zenkov, N.K., et al., Okislitel’nyi stress. Prooksidanty i antioksidanty (Oxidative Stress. Prooxidants and Antioxidants), Moscow: Slovo, 2006.

  61. Milzani, A., Rossi, R., Di Simplicio, P., et al., The oxidation produced by hydrogen peroxide on Ca-ATP-G-actin, Protein Sci., 2000, vol. 9, pp. 1774–1782.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Misztal, T., Golaszewska, A., Tomasiak-Lozowska, M.M., et al., The myeloperoxidase product, hypochlorous acid, reduces thrombus formation under flow and attenuates clot retraction and fibrinolysis in human blood, Free Radical Biol. Med., 2019, vol. 141, pp. 426–437.

    Article  CAS  Google Scholar 

  63. Moskovitz, J., Berlett, B.S., Poston, J.M., and Stadtman, E.R., The yeast peptide-methionine sulfoxide reductase functions as an antioxidant in vivo, Proc. Natl. Acad. Sci. U.S.A., 1997, vol. 94, pp. 9585–9589.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Moskovitz, J., Flescher, E., Berlett, B.S., et al., Overexpression of peptide-methionine sulfoxide reductase in Saccharomyces cerevisiae and human T cells provides them with high resistance to oxidative stress, Proc. Natl. Acad. Sci. U.S.A., 1998, vol. 95, pp. 14071–14075.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Moskovitz, J., Levine, R.L., and Stadtman, E.R., Oxidation of methionine in proteins roles in antioxidant defense and cellular regulation, IUBMB Life, 2000, vol. 50, pp. 301–317.

    Article  PubMed  Google Scholar 

  66. Moskovitz, J., Bar-Noy, S., Williams, W.M., et al., Methionine sulfoxide reductase (MsrA) is a regulator of antioxidant defense and lifespan in mammals, Proc. Natl. Acad. Sci. U.S.A., 2001, vol. 98, pp. 12920–12925.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Nimalaratne, C. and Wu, J., Hen egg as an antioxidant food commodity: a review, Nutrients, 2015, vol. 7, pp. 8274–8293.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Nishinaka, Y., Masutani, H., Nakamura, H., and Yodoi, J., Regulatory roles of thioredoxin in oxidative stress-induced cellular responses, Redox Rep., 2001, vol. 6, pp. 289–295.

    Article  CAS  PubMed  Google Scholar 

  69. Oda, T., Iwasa, M., Aihara, T., et al., The nature of the globular- to fibrous-actin transition, Nature, 2009, vol. 457, pp. 441–445.

    Article  CAS  PubMed  Google Scholar 

  70. Olson, S.T. and Björk, I., Regulation of thrombin activity by antithrombin and heparin, Sem. Thromb. Haemostasis, 1994, vol. 20, pp. 373–409.

    Article  CAS  Google Scholar 

  71. Olson, S.T., Swanson, R., Raub-Segall, E., et al., Accelerating ability of synthetic oligosaccharides on antithrombin inhibition of proteinases of the clotting and fibrinolytic systems. Comparison with heparin and low-molecular-weight heparin, Thromb. Haemostasis, 2004, vol. 92, pp. 929–939.

    Article  CAS  Google Scholar 

  72. Panasenko, O.M., Gorudko, I.V., and Sokolov, A.V., Hypochlorous acid as a precursor of free radicals in living systems, Usp. Biol. Khim., 2013, vol. 53, pp. 195–244.

    Google Scholar 

  73. Pederson, E.N. and Interlandi, G., Oxidation-induced destabilization of the fibrinogen αC-domain dimer investigated by molecular dynamics simulations, Proteins, 2019, vol. 87, pp. 826–836.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Poljšak, B. and Fink, R., The protective role of antioxidants in the defence against ROS/RNS-mediated environmental pollution, Oxid. Med. Cell. Longevity, 2014, vol. 2014, pp. 1–22.

    Article  Google Scholar 

  75. Protopopova, A.D., Ramirez, A., Klinov, D.V., et al., Factor XIII topology: organization of B subunits and changes with activation studied with single-molecule atomic force microscopy, J. Thromb. Haemostasis, 2019, vol. 17, pp. 737–748.

    Article  Google Scholar 

  76. Qin, Z. and Squier, T.C., Calcium-dependent stabilization of the central sequence between Met(76) and Ser(81) in vertebrate calmodulin, Biophys. J., 2001, vol. 81, pp. 2908–2918.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Rau, J.C., Beaulieu, L.M., Huntington, J.A., and Church, F.C., Serpins in thrombosis, hemostasis and fibrinolysis, J. Thromb. Haemostasis, 2007, vol. 5, suppl. 1, pp. 102–115.

    Article  CAS  Google Scholar 

  78. Ray, P.D., Huang, B.-W., and Tsuji, Y., Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling, Cell. Signaling, 2012, vol. 24, pp. 981–990.

    Article  CAS  Google Scholar 

  79. Reddy, V.Y., Desorchers, P.E., Pizzo, S.V., et al., Oxidative dissociation of human α2-macroglobulin tetramers into dysfunctional dimers, J. Biol. Chem., 1994, vol. 269, pp. 4683–4691.

    Article  CAS  PubMed  Google Scholar 

  80. Rehman, A.A., Ahsan, H., and Khan, F.H., α2-Macroglobulin: a physiological guardian, J. Cell. Physiol., 2013, vol. 8, pp. 1665–1675.

    Article  Google Scholar 

  81. Rijken, D.C. and Uitte de Willige, S., Inhibition of fibrinolysis by coagulation factor XIII, Biomed. Res. Int., 2017, vol. 2017, art. ID 1209676.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Rizzo, A.M., Berselli, P., Zava, S., et al., Endogenous antioxidants and radical scavengers, Adv. Exp. Med. Biol., 2010, vol. 698, pp. 52–67.

    Article  CAS  PubMed  Google Scholar 

  83. Rivett, A.J., Regulation of intracellular protein turnover: covalent modification as a mechanism of marking proteins for degradation, Curr. Top. Cell. Reg., 1986, vol. 28, pp. 291–337.

    Article  CAS  Google Scholar 

  84. Rosenfeld, M.A., Bychkova, A.V., Shchegolikhin, A.N., et al., Ozone-induced oxidative modification of plasma fibrin-stabilizing factor, Biochim. Biophys. Acta, Proteins Proteomics, 2013, vol. 1834, pp. 2470–2479.

    Article  CAS  Google Scholar 

  85. Rosenfeld, M.A, Vasilyeva, A.D., Yurina, L.V., et al., Oxidation of proteins: is it a programmed process? Free Radical Res., 2018, vol. 52, pp. 14–38.

    Article  CAS  Google Scholar 

  86. Ruan, H., Tang, X.D., Chen, M.L., et al., High-quality life extension by the enzyme peptide methionine sulfoxide reductase, Proc. Natl. Acad. Sci. U.S.A., 2002, vol. 99, pp. 2748–2753.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Shacter, E., Williams, J.A., and Lim, M., Differential susceptibility of plasma proteins to oxidative modification: examination by Western blot immunoassay, Free Radical Biol. Med., 1994, vol. 17, pp. 429–436.

    Article  CAS  Google Scholar 

  88. Sigalov, A.B. and Stern, L.J., Enzymatic repair of oxidative damage to human apolipoprotein A-I, FEBS Lett., 1998, vol. 433, pp. 196–200.

    Article  CAS  PubMed  Google Scholar 

  89. Simiczyjew, A., Mazur, A.J., Dratkiewicz, E., and Nowak, D., Involvement of β- and γ-actin isoforms in actin cytoskeleton organization and migration abilities of bleb-forming human colon cancer cells, PLoS One, 2017, vol. 12, p. e0173709.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Souri, M., Kaetsu, H., and Ichinose, A., Sushi domains in the subunit-B of factor XIII responsible for oligomer assembly, Biomolecules, 2008, vol. 47, pp. 8656–8664.

    CAS  Google Scholar 

  91. Souri, M., Osaki, T., and Ichinose, A., The non-catalytic B subunit of coagulation actor XIII accelerates fibrin cross-linking, J. Biol. Chem., 2015, vol. 290, pp. 12027–12039.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Sovová, Ž., Štikarová, J., Kaufmanová, J., et al., Impact of posttranslational modifications on atomistic structure of fibrinogen, PLoS One, 2020, vol. 15, p. e0227543.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Spahr, C.S., Nahri, L., Speakman, J., et al., The effects of in vitro methionine oxidation on the bioactivity and structure of human keratinocyte growth factor, Protein Sci., 1996, vol. 5, pp. 299–308.

    Google Scholar 

  94. Stadtman, E.R. and Levine, R.L., Free radical-mediated oxidation of free amino acids and amino acid residues in proteins, Amino Acids, 2003, vol. 25, pp. 207–218.

    Article  CAS  PubMed  Google Scholar 

  95. Stief, T.W., Aab, A., and Heimburger, N., Oxidative inactivation of purified human alpha-2-antiplasmin, antithrombin III, and C1-inhibitor, Thromb. Res., 1988, vol. 49, pp. 581–589.

    Article  CAS  PubMed  Google Scholar 

  96. Stief, T.W., Kurz, J., Doss, M.O., and Fareed, J., Singlet oxygen inactivates fibrinogen, factor V, factor VIII, factor X, and platelet aggregation of human blood, Thromb. Res., 2000, vol. 97, pp. 473–480.

    Article  CAS  PubMed  Google Scholar 

  97. Stournaras, C., Drewes, G., Blackholm, H., et al., Glutathionyl(cysteine-374) actin forms filaments of low mechanical stability, Biochim. Biophys. Acta, Protein Struct. Mol. Enzymol., 1990, vol. 1037, pp. 86–91.

    Article  CAS  Google Scholar 

  98. Tarrago, L., Kaya, A., Weerapana, E., et al., Methionine sulfoxide reductases preferentially reduce unfolded oxidized proteins and protect cells from oxidative protein unfolding, J. Biol. Chem., 2012, vol. 287, pp. 24448–24459.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Tebar, F., Chavero, A., Agell, N., et al., Pleiotropic roles of calmodulin in the regulation of KRas and Rac1 GTPases: functional diversity in health and disease, Int. J. Mol. Sci., 2020, vol. 21, p. 3680.

    Article  CAS  PubMed Central  Google Scholar 

  100. Tse, G., Yan, B.P., Chan, Y.W., et al., Reactive oxygen species, endoplasmic reticulum stress and mitochondrial dysfunction: the link with cardiac arrhythmogenesis, Front. Physiol., 2016, vol. 7, p. 313.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Tsurupa, G., Pechik, I., Litvinov, R.I., et al., On the mechanism of αC polymer formation in fibrin, Biochemistry, 2012, vol. 51, pp. 2526–2538.

    Article  CAS  PubMed  Google Scholar 

  102. van Patten, S.M., Hanson, E., Bernasconi, R., et al., Oxidation of methionine residues in antithrombin. Effects on biological activity and heparin binding, J. Biol. Chem., 1999, vol. 274, pp. 10268–10276.

    Article  CAS  PubMed  Google Scholar 

  103. Vasilyeva, A., Indeykina, M., Bychkova, A., et al., Oxidation-induced modifications of the catalytic subunits of plasma fibrin-stabilizing factor at the different stages of its activation identified by mass spectrometry, Biochim. Biophys. Acta, Proteins Proteomics, 2018, vol. 1866, pp. 875–884.

    Article  CAS  PubMed  Google Scholar 

  104. Vasilyeva, A., Yurina, L., Shchegolikhin, A., et al., The structure of blood coagulation factor XIII is adapted to oxidation, Biomolecules, 2020, vol. 10, p. 914.

    Article  CAS  PubMed Central  Google Scholar 

  105. Veredas, F.J., Aledo, J.C., and Cantón, F.R., Methionine residues around phosphorylation sites are preferentially oxidized in vivo under stress conditions, Sci. Rep., 2017, vol. 7, p. 40403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Vetter, S.W. and Leclerc, E., Novel aspects of calmodulin target recognition and activation, Eur. J. Biochem., 2003, vol. 270, pp. 404–414.

    Article  CAS  PubMed  Google Scholar 

  107. Vogt, W., Oxidation of methionyl residues in proteins: tools, targets, and reversal, Free Radical Biol. Med., 1995, vol. 18, pp. 93–105.

    Article  CAS  Google Scholar 

  108. Walgenbach, D.G., Gregory, A.J., and Klein, J.C., Unique methionine-aromatic interactions govern the calmodulin redox sensor, Biochem. Biophys. Res. Commun., 2018, vol. 20, pp. 236–241.

    Article  Google Scholar 

  109. Walker E.J., Bettinger J.Q., Welle K.A., et al., Global analysis of methionine oxidation provides a census of folding stabilities for the human proteome, Proc. Natl. Acad. Sci. U.S.A., 2019, vol. 116, pp. 6081–6090.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Wang, J., Boja, E.S., Tan, W., et al., Reversible glutathionylation regulates actin polymerization in A431 cells, J. Biol. Chem., 2001, vol. 276, pp. 47763–47766.

    Article  CAS  PubMed  Google Scholar 

  111. Wang, P., Wu, Y., Li, X., et al., Thioredoxin and thioredoxin reductase control tissue factor activity by thiol redox-dependent mechanism, J. Biol. Chem., 2013, vol. 288, pp. 3346–3358.

    Article  CAS  PubMed  Google Scholar 

  112. Wang, Q. and Zennadi, R., Oxidative stress and thrombosis during aging: the roles of oxidative stress in RBCS in venous thrombosis, Int. J. Mol. Sci., 2020, vol. 21, p. 4259.

    Article  CAS  PubMed Central  Google Scholar 

  113. Wang, Z., Feng, B., Xiao, G., and Zhou, Z., Roles of methionine oxidation in E200K prion protein misfolding: implications for the mechanism of pathogenesis in E200K linked familial Creutzfeldt–Jakob disease, Biochim. Biophys. Acta, Proteins Proteomics, 2016, vol. 1864, pp. 346–358.

    Article  CAS  Google Scholar 

  114. Weigandt, K.M., White, N., Chung, D., et al., Fibrin clot structure and mechanics associated with specific oxidation of methionine residues in fibrinogen, Biophys. J., 2012, vol. 103, pp. 2399–2407.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Weisel, J.W. and Litvinov, R.I., Fibrin formation, structure and properties, Subcell. Biochem., 2017, vol. 82, pp. 405−456.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Weissbach, H., Resnick, I., and Brot, N., Methionine sulfoxide reductases: history and cellular role in protecting against oxidative damage, Biochim. Biophys. Acta, Proteins Proteomics, 2005, vol. 1703, pp. 203–212.

    Article  CAS  Google Scholar 

  117. White, N.J., Wang, Y., Fu, X., et al., Post-translational oxidative modification of fibrinogen is associated with coagulopathy after traumatic injury, Free Radical Biol. Med., 2016, vol. 96, pp. 181–189.

    Article  CAS  Google Scholar 

  118. Wilson, C., Terman, J.R., González-Billault, C., and Ahmed, G., Actin filaments—a target for redox regulation, Cytoskeleton, 2016, vol. 73, pp. 577–595.

    Article  CAS  PubMed  Google Scholar 

  119. Wu, S.M., Patel, D.D., and Pizzo, S.V., Oxidized α2-macroglobulin (α2M) differentially regulates receptor binding by cytokines/growth factors: implications for tissue injury and repair mechanisms in inflammation, J. Immunol., 1998, vol. 161, pp. 4356–4365.

    Article  CAS  PubMed  Google Scholar 

  120. Wyatt, A.R., Kumita, J.R., Farrawell, N.E., et al., Alpha-2-macroglobulin is acutely sensitive to freezing and lyophilization: implications for structural and functional studies, PLoS One, 2015, vol. 10, p. e0130036.

    Article  PubMed  PubMed Central  Google Scholar 

  121. Wyatt, A.R., Kumita, J.R., Mifsud, R.W., et al., Hypochlorite-induced structural modifications enhance the chaperone activity of human α2-macroglobulin, Proc. Natl. Acad. Sci. U.S.A., 2014, vol. 111, pp. 2081–2090.

    Article  Google Scholar 

  122. Xu, K., Uversky, V.N., and Xue, B., Local flexibility facilitates oxidization of buried methionine residues, Protein Pept. Lett., 2012, vol. 19, pp. 688–697.

    Article  CAS  PubMed  Google Scholar 

  123. Xu, Q., Huff, L.P., Fujii, M., and Griendling, K.K., Redox regulation of the actin cytoskeleton and its role in the vascular system, Free Radical Biol. Med., 2017, vol. 109, pp. 84–107.

    Article  CAS  Google Scholar 

  124. Yamniuk, A.P. and Vogel, H.J., Calmodulin’s flexibility allows for promiscuity in its interactions with target proteins and peptides, Mol. Biotechnol., 2004, vol. 27, pp. 33–57.

    Article  CAS  PubMed  Google Scholar 

  125. Yermolaieva, O., Xu, R., Schinstock, C., et al., Methionine sulfoxide reductase A protects neuronal cells against brief hypoxia/reoxygenation, Proc. Natl. Acad. Sci. U.S.A., 2004, vol. 101, pp. 1159–1164.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Yurina, L.V., Vasilyeva, A.D., Bugrova, A.E., et al., Hypochlorite-induced oxidative modification of fibrinogen, Dokl. Biochem. Biophys., 2019a, vol. 484, no. 1, pp. 37–41.

    Article  CAS  PubMed  Google Scholar 

  127. Yurina, L., Vasilyeva, A., Indeykina, M., et al., Ozone-induced damage of fibrinogen molecules: identification of oxidation sites by high-resolution mass spectrometry, Free Radical Res., 2019b, vol. 53, pp. 430–455.

    Article  CAS  Google Scholar 

  128. Yurina, L.V., Vasilyeva, A.D., Kononenko, V.L., et al., The structural-functional damage of fibrinogen oxidized by hydrogen peroxide, Dokl. Biochem. Biophys., 2020, vol. 492, no. 1, pp. 130–134.

    Article  CAS  PubMed  Google Scholar 

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ACKNOWLEDGMENTS

The authors are grateful to anonymous reviewer for valuable comments that contributed to improvement of the quality of publication.

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This work was supported in part by the Russian Foundation for Basic Research, project no. 18-04-01313.

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  1. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Moscow, Russia

    M. A. Rosenfeld, L. V. Yurina & A. D. Vasilyeva

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  1. M. A. Rosenfeld
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Rosenfeld, M.A., Yurina, L.V. & Vasilyeva, A.D. Functional Role of Methionine Oxidation in Proteins: Arguments for and against. Biol Bull Rev 11 (Suppl 1), 1–18 (2021). https://doi.org/10.1134/S2079086421070070

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