Репарация белков с участием PIMT: механизм и значение

Сноски

* Адресат для корреспонденции.

Благодарности

Авторы благодарят директора Индийского научно-исследовательского ветеринарного института и NFBSFARA за предоставление необходимых финансовых средств и услуг для работ по изучению PIMT, выполненных в лаборатории Mahawar.

Вклад авторов

Mishra P.K.K. — сбор данных, построение филогенетических деревьев, моделирование белков, составление таблиц и подготовка черновой версии статьи; Mahawar M. — исправления и доработка черновой версии статьи.

Конфликт интересов

Авторы заявляют об отсутствии конфликта интересов.

Соблюдение этических норм

Настоящая статья не содержит описания выполненных авторами исследований с участием людей или использованием животных в качестве объектов.

Список литературы

1. Paik, W.K., and Kim, S. (1971) Protein methylation, Science, 174, 117–119.

2. Paik, W.K., and Kim, S. (2007) Historical review: the field of protein methylation, Trends Biochem. Sci., 32, 146–152.

3. Ambler, R.P., and Rees, M.W. (1959) ε-N-Methyl-lysine in bacterial flagellar protein, Nature, 184, 56–57.

4. Murray, K. (1964) The occurrence of е-N-methyl lysine in histones, Biochemistry, 3, 10–15.

5. Kuehl, W.M., and Adelstein, R.S. (1970) The absence of 3-methylhistidine in red, cardiac and fetal myosins, Biochem. Biophys. Res. Commun., 39, 956–964.

6. Weihing, R.R., and Korn, E.D. (1970) ε-N-Dimethyllysine in amoeba actin, Nature, 227, 1263–1264.

7. Kakimoto, Y., and Akazawa, S. (1970) Isolation and identification of NG, NG- and NG, N’G-dimethylarginine, Nе-mono-, di-, and trimethyllysine, and glucosylgalactosyl- and galactosyl-δ-hydroxylysine from human urine, J. Biol. Chem., 245, 5751–5758.

8. Johnson, P., Harris, C.I., and Perry, S.V. (1967) 3-Methylhistidine in actin and other muscle proteins, Biochem. J., 105, 361–370.

9. Asatoor, A.M., and Armstrong, M.D. (1967) 3-Methylhistidine, a component of actin, Biochem. Biophys. Res. Comm., 26, 168–174.

10. Liss, M., Maxam, A.M., and Cuprak, L.J. (1969) Methylation of protein by calf spleen methylase a new protein methylation reaction, J. Biol. Chem., 244, 1617–1622.

11. Kleinsmith, L.J., Allfrey, V.G., and Mirsky, A.E. (1966) Phosphoprotein metabolism in isolated lymphocyte nuclei, Proc. Natl. Acad. Sci. USA, 55, 1182–1189.

12. Clarke, S. (1993) Protein methylation, Curr. Opin. Cell Biol., 5, 977–983.

13. Clarke, S.G. (2013) Protein methylation at the surface and buried deep: thinking outside the histone box, Trends Biochem. Sci., 38, 243–252.

14. Visick, J.E., Cai, H., and Clarke, S. (1998) The L-isoaspartyl protein repair methyltransferase enhances survival of aging Escherichia coli subjected to secondary environmental stresses, J. Bacteriol., 180, 2623–2629.

15. Li, C., and Clarke, S. (1992) A protein methyltransferase specific for altered aspartyl residues is important in Escherichia coli stationary-phase survival and heat-shock resistance, Proc. Natl. Acad. Sci. USA, 89, 9885–9889.

16. Visick, J.E., and Clarke, S. (1995) Repair, refold, recycle: how bacteria can deal with spontaneous and environmental damage to proteins, Mol. Microbiol., 16, 835–845.

17. Nguyen, V.T., Morange, M., and Bensaude, O. (1989) Protein denaturation during heat shock and related stress. Escherichia coli β-galactosidase and Photinus pyralis luciferase inactivation in mouse cells, J. Biol. Chem., 264, 10487–10492.

18. Stadtman, E.R. (1992) Protein oxidation and aging, Science, 257, 1220–1224.

19. Reissner, K.J., and Aswad, D.W. (2003) Deamidation and isoaspartate formation in proteins: unwanted alterations or surreptitious signals? Cell. Mol. Life Sci., 60, 1281–1295.

20. Clarke, S. (1999) A protein carboxyl methyltransferase that recognizes age-damaged peptides and proteins and participates in their repair, in S-Adenosylmethionine-dependent methyltransferases: structures and functions (Xiaodong, C., and Blumenthal, R.M., eds), World Scientific, Singapore, pp. 123–148.

21. Skinner, M.M., Puvathingal, J.M., Walter, R.L., and Friedman, A.M. (2000) Crystal structure of protein isoaspartyl methyltransferase: a catalyst for protein repair, Structure, 8, 1189–1201.

22. McFadden, P.N., and Clarke, S. (1987) Conversion of isoaspartyl peptides to normal peptides: implications for the cellular repair of damaged proteins, Proc. Natl. Acad. Sci. USA, 84, 2595–2599.

23. Geiger, T., and Clarke, S. (1987) Deamidation, isomerization, and racemization at asparaginyl and aspartyl residues in peptides, J. Biol. Chem., 26, 2785–2794.

24. Momand, J.A., and Clarke, S. (1990) The fidelity of protein synthesis: can mischarging by aspartyl-tRNA(Asp) synthetase lead to the formation of isoaspartyl residues in proteins? Biochim. Biophys. Acta, 1040, 153–158.

25. Lowenson, J.D., and Clarke, S. (1992) Recognition of D-aspartyl residues in polypeptides by the erythrocyte L-isoaspartyl/D-aspartyl protein methyltransferase. Implications for the repair hypothesis, J. Biol. Chem., 267, 5985–5995.

26. Levine, R.L., Moskovitz, J., and Stadtman, E.R. (2000) Oxidation of methionine in proteins: roles in antioxidant defense and cellular regulation, IUBMB Life, 50, 301–307.

27. Chondrogianni, N., Petropoulos, I., Grimm, S., Georgila, K., Catalgol, B., Friguet, B., Grune, T., and Gonos, E.S. (2014) Protein damage, repair and proteolysis, Mol. Aspects Med., 35, 1–71.

28. Johnson, B.A., and Aswad, D.W. (1993) Kinetic properties of bovine brain protein L-isoaspartyl methyltransferase determined using a synthetic isoaspartyl peptide substrate, Neurochem. Res., 18, 87–94.

29. Yang, H., and Zubarev, R.A. (2010) Mass spectrometric analysis of asparagine deamidation and aspartate isomerization in polypeptides, Electrophoresis, 31, 1764–1772.

30. Alfaro, J.F., Gillies, L.A., Sun, H.G., Dai, S., Zang, T., Klaene, J.J., Kim, B.J., Lowenson, J.D., Clarke, S.G., Karger, B.L., and Zhou, Z.S. (2008) Chemo-enzymatic detection of protein isoaspartate using protein isoaspartate methyltransferase and hydrazine trapping, Anal. Chem., 80, 3882–3889.

31. Kameoka, D., Ueda, T., and Imoto, T. (2003) A method for the detection of asparagine deamidation and aspartate isomerization of proteins by MALDI/TOF-mass spectrometry using endoproteinase Asp-N, J. Biochem., 134, 129–135.

32. Lehmann, W.D., Schlosser, A., Erben, G., Pipkorn, R., Bossemeyer, D., and Kinzel, V. (2000) Analysis of isoaspartate in peptides by electrospray tandem mass spectrometry, Protein Sci., 9, 2260–2268.

33. Cournoyer, J.J., Lin, C., and O’Connor, P.B. (2006) Detecting deamidation products in proteins by electron capture dissociation, Anal. Chem., 78, 1264–1271.

34. Ni, W., Dai, S., Karger, B.L., and Zhou, Z.S. (2010) Analysis of isoaspartic acid by selective proteolysis with Asp-N and electron transfer dissociation mass spectrometry, Anal. Chem., 82, 7485–7491.

35. Liu, M., Cheetham, J., Cauchon, N., Ostovic, J., Ni, W., Ren, D., and Zhou, Z.S. (2011) Protein isoaspartate methyltransferase-mediated 18O-labeling of isoaspartic acid for mass spectrometry analysis, Anal. Chem., 84, 1056–1062.

36. MacLaren, D.C., and Clarke, S. (1995) Expression and purification of a human recombinant methyltransferase that repairs damaged proteins, Protein Expr. Purif., 6, 99–108.

37. Brennan, T.V., and Clarke, S. (1993) Spontaneous degradation of polypeptides at aspartyl and asparaginyl residues: effects of the solvent dielectric, Protein Sci., 2, 331–338.

38. Brennan, T.V., and Clarke, S. (1995) Effect of adjacent histidine and cysteine residues on the spontaneous degradation of asparaginyl- and aspartyl-containing peptides, Int. J. Pept. Protein Res., 45, 547–553.

39. Sharma, S., Hammen, P.K., Anderson, J.W., Leung, A., Georges, F., Hengstenberg, W., Klevit, R.E., and Waygood, E.B. (1993) Deamidation of HPr, a phosphocarrier protein of the phosphoenolpyruvate: sugar phosphotransferase system, involves asparagine 38 (HPr-1) and asparagine 12 (HPr-2) in isoaspartyl acid formation, J. Biol. Chem., 268, 17695–17704.

40. Hicks, W.M., Kotlajich, M.V., and Visick, J.E. (2005) Recovery from long-term stationary phase and stress survival in Escherichia coli require the L-isoaspartyl protein carboxyl methyltransferase at alkaline pH, Microbiology, 151, 2151–2158.

41. Lyon, Y.A., Sabbah, G.M., and Julian, R.R. (2018) Differences in α-crystallin isomerization reveal the activity of protein isoaspartyl methyltransferase (PIMT) in the nucleus and cortex of human lenses, Exp. Eye Res., 171, 131–141.

42. Vigneswara, V., Lowenson, J.D., Powell, C.D., Thakur, M., Bailey, K., Clarke, S., and Carter, W.G. (2006) Proteomic identification of novel substrates of a protein isoaspartyl methyltransferase repair enzyme, J. Biol. Chem., 281, 32619–32629.

43. Kagan, R.M., and Clarke, S. (1994) Widespread occurrence of three sequence motifs in diverse S-adenosylmethionine-dependent methyltransferases suggests a common structure for these enzymes, Arch. Biochem. Biophys., 310, 417–427.

44. Lowenson, J.D., and Clarke, S. (1991) Spontaneous degradation and enzymatic repair of aspartyl and asparaginyl residues in aging red cell proteins analyzed by computer simulation, Gerontology, 37, 128–151.

45. Ryttersgaard, C., Griffith, S.C., Sawaya, M.R., MacLaren, D.C., Clarke, S., and Yeates, T.O. (2002) Crystal structure of human L-isoaspartyl methyltransferase, J. Biol. Chem., 277, 10642–10646.

46. Dutta, T., Banerjee, S., Soren, D., Lahiri, S., Sengupta, S., Rasquinha, J.A., and Ghosh, A.K. (2012) Regulation of enzymatic activity by deamidation and their subsequent repair by protein L-isoaspartyl methyl transferase, Appl. Biochem Biotechnol., 168, 2358–2375.

47. Chatterjee, T., Mukherjee, D., Banerjee, M., Chatterjee, B.K., and Chakrabarti, P. (2015) Crystal structure and activity of protein L-isoaspartyl-O-methyltransferase from Vibrio cholerae, and the effect of AdoHcy binding, Arch. Biochem. Biophys., 583, 140–149.

48. Oda, A., Noji, I., Fukuyoshi, S., and Takahashi, O. (2015) Prediction of binding modes between protein L-isoaspartyl (D-aspartyl) O-methyltransferase and peptide substrates including isomerized aspartic acid residues using in silico analytic methods for the substrate screening, J. Pharm. Biomed. Anal., 116, 116–122.

49. Bennett, E.J., Bjerregaard, J., Knapp, J.E., Chavous, D.A., Friedman, A.M., Royer, W.E., and O’Connor, C.M. (2003) Catalytic implications from the Drosophila protein L-isoaspartyl methyltransferase structure and site-directed mutagenesis, Biochemistry, 42, 12844–12853.

50. Kim, J., Chen, B., Bru, J.L., Huynh, E., Momen, M., and Aswad, D.W. (2018) New findings on SNP variants of human protein L-isoaspartyl methyltransferase that affect catalytic activity, thermal stability, and aggregation, PLoS One, 13, e0198266.

51. Mudgett, M.B., and Clarke, S. (1993) Characterization of plant L-isoaspartyl methyltransferases that may be involved in seed survival: purification, cloning, and sequence analysis of the wheat germ enzyme, Biochemistry, 32, 11100–11111.

52. Fujii, N., Satoh, K., Harada, K.Y., and Ishibashi, Y. (1994) Simultaneous stereoinversion and isomerization at specific aspartic acid residues in αA-crystallin from human lens, J. Biochem., 116, 663–669.

53. Verma, P., Kaur, H., Petla, B.P., Rao, V., Saxena, S.C., and Majee, M. (2013) Protein L-isoaspartyl methyltransferase 2 gene is differentially expressed in chickpea and enhances seed vigor and longevity by reducing abnormal isoaspartyl accumulation predominantly in seed nuclear proteins, Plant Physiol., 161, 1141–1157.

54. Zheng, Q.X., Fu, H.Y., Li, H.D., Wang, B., Peng, C.H., Wang, S., Cai, J.L., Liu, S.F., Zhang, X.B., and Yu, Y.J. (2017) Automatic time-shift alignment method for chromatographic data analysis, Sci. Rep., 7, 256.

55. Nascimento, E.D.S., and Tenuta Filho, A. (2010) Chemical waste risk reduction and environmental impact generated by laboratory activities in research and teaching institutions, Brazil. J. Pharmac. Sci., 46, 187–198.

56. Itoh, T. (2012) Fluorescence and phosphorescence from higher excited states of organic molecules, Chem. Rev., 112, 4541–4568.

57. Kimura, Y., Komatsu, T., Yanagi, K., Hanaoka, K., Ueno, T., Terai, T., Kojima, H., Okabe, T., Nagano, T., and Urano, Y. (2017) Development of chemical tools to monitor and control isoaspartyl peptide methyltransferase activity, Angew. Chem. Int. Ed. Engl., 56, 153–157.

58. Fu, J.C., Ding, L., and Clarke, S. (1991) Purification, gene cloning, and sequence analysis of an L-isoaspartyl protein carboxyl methyltransferase from Escherichia coli, J. Biol. Chem., 266, 14562–14572.

59. Kagan, R.M., McFadden, H.J., McFadden, P.N., O’Connor, C., and Clarke, S. (1997) Molecular phylogenetics of a protein repair methyltransferase, Compar. Biochem. Physiol. B Biochem. Mol. Biol., 117, 379–385.

60. Saito, H., Yamashita, M., Ogasawara, M., Yamada, N., Niisato, M., Deguchi, M.H., Tanita, T., Ishida, K., Sugai, T., and Yamauchi, K. (2016) Chaperone protein L-isoaspartate (D-aspartyl) O-methyltransferase as a novel predictor of poor prognosis in lung adenocarcinoma, Hum. Pathol., 50, 1–10.

61. Johnson, B.A., Ngo, S.Q., and Aswad, D.W. (1991) Widespread phylogenetic distribution of a protein methyltransferase that modifies L-isoaspartyl residues, Biochem. Int., 24, 841–847.

62. Johnson, B.A., Shirokawa, J.M., Hancock, W.S., Spellman, M.W., Basa, L.J., and Aswad, D.W. (1989) Formation of isoaspartate at two distinct sites during in vitro aging of human growth hormone, J. Biol. Chem., 264, 14262–14271.

63. Ichikawa, J.K., and Clarke, S. (1998) A highly active protein repair enzyme from an extreme thermophile: the L-isoaspartyl methyltransferase from Thermotoga maritima, Arch. Biochem. Biophys., 358, 222–231.

64. Li, C., and Clarke, S. (1992) Distribution of an L-isoaspartyl protein methyltransferase in eubacteria, J. Bacteriol., 174, 355–361.

65. Xu, Q., Belcastro, M.P., Villa, S.T., Dinkins, R.D., Clarke, S.G., and Downie, A.B. (2004) A second protein L-isoaspartyl methyltransferase gene in Arabidopsis produces two transcripts whose products are sequestered in the nucleus, Plant Physiol., 136, 2652–2664.

66. Mudgett, M.B., and Clarke, S. (1994) Hormonal and environmental responsiveness of a developmentally regulated protein repair L-isoaspartyl methyltransferase in wheat, J. Biol. Chem., 269, 25605–25612.

67. Mudgett, M.B., Lowenson, J.D., and Clarke, S. (1997) Protein repair L-isoaspartyl methyltransferase in plants (phylogenetic distribution and the accumulation of substrate proteins in aged barley seeds), Plant Physiol., 115, 1481–1489.

68. Clarke, S. (1987) Propensity for spontaneous succinimide formation from aspartyl and asparaginyl residues in cellular proteins, Int. J. Pept. Protein Res., 30, 808–821.

69. DeVry, C.G., and Clarke, S. (1999) Polymorphic forms of the protein L-isoaspartate (D-aspartate) O-methyltransferase involved in the repair of age-damaged proteins, J. Hum. Genet., 44, 275–288.

70. Juang, C., Chen, B., Bru, J.L., Nguyen, K., Huynh, E., Momen, M., Kim, J., and Aswad, D.W. (2017) Polymorphic variants of human protein L-isoaspartyl methyltransferase affect catalytic activity, aggregation, and thermal stability; implications for the etiology of neurological disorders and cognitive aging, J. Biol. Chem., 292, 3656–3665.

71. Rutherford, K., and Daggett, V. (2009) The V119I polymorphism in protein L-isoaspartate O-methyltransferase alters the substrate-binding interface, Protein Eng. Des. Sel., 22, 713–721.

72. Pesingi, P.K., Kumawat M., Behera P., Dixit, S.K., Agarwal, R.K., Goswami, T.K., and Mahawar, M. (2017) Protein-L-isoaspartyl methyltransferase (PIMT) is required for survival of Salmonella typhimurium at 42 °C and contributes to the virulence in poultry, Front. Microbiol., 8, 361.

73. Kumawat, M., Pesingi, P.K., Agarwal, R.K, Goswami, T.K., and Mahawar, M. (2016) Contribution of protein isoaspartate methyl transferase (PIMT) in the survival of Salmonella typhimurium under oxidative stress and virulence, Int. J. Med. Microbiol., 306, 222–230.

74. VandenBerg, K.E., Ahn, S., and Visick, J.E. (2016) (p)ppGpp-Dependent persisters increase the fitness of Escherichia coli bacteria deficient in isoaspartyl protein repair, Appl. Environ. Microbiol., 825, 5444–5454.

75. Qin, Z., Zhu, J.X., and Aswad, D.W. (2016) The D-isoAsp-25 variant of histone H2B is highly enriched in active chromatin: potential role in the regulation of gene expression? Amino Acids, 48, 599–603.

76. Villa, S.T., Xu, Q., Downie, A.B., and Clarke, S.G. (2006) Arabidopsis protein repair L-isoaspartyl methyltransferases: predominant activities at lethal temperatures, Physiol. Plant., 128, 581–592.

77. Ladino, C.A., and O’Connor, C.M. (1992) Methylation of atypical protein aspartyl residues during the stress response of HeLa cells, J. Cell. Physiol., 153, 297–304.

78. Petla, B.P., Kamble, N.U., Kumar, M., Verma, P., Ghosh, S., Singh, A., Rao, V., Saxena, S.C., Salvi, P., Kaur, H., and Majee, M. (2016) Rice protein L-isoaspartyl methyltransferase isoforms differentially accumulate during seed maturation to restrict deleterious isoAsp and reactive oxygen species accumulation and are implicated in seed vigor and longevity, New Phytol., 211, 627–645.

79. Warmack, R.A., Mansilla, E., Goya, R.G., and Clarke, S.G. (2016) Racemized and isomerized proteins in aging rat teeth and eye lens, Rejuvenation Res., 19, 309–317.

80. Kim, E., Lowenson, J.D., MacLaren, D.C., Clarke, S., and Young, S.G. (1997) Deficiency of a protein-repair enzyme results in the accumulation of altered proteins, retardation of growth, and fatal seizures in mice, Proc. Natl. Acad. Sci. USA, 94, 6132–6137.

81. Dimitrijevic, A., Qin, Z., and Aswad, D.W. (2014) Isoaspartyl formation in creatine kinase B is associated with loss of enzymatic activity; implications for the linkage of isoaspartate accumulation and neurological dysfunction in the PIMT knockout mouse, PLoS One, 9, e100622.

82. Khare, S., Gomez, T., Linster, C.L., and Clarke, S.G. (2009) Defective responses to oxidative stress in protein L-isoaspartyl repair-deficient Caenorhabditis elegans, Mech. Ageing Dev., 130, 670–680.

83. Brennan, T.V., Anderson, J.W., Jia, Z., Waygood, E.B., and Clarke, S. (1994) Repair of spontaneously deamidated HPr phosphocarrier protein catalyzed by the L-isoaspartate-(D-aspartate) O-methyltransferase, J. Biol. Chem., 269, 24586–24595.

84. Zhu, J.X., Doyle, H.A., Mamula, M.J., and Aswad, D.W. (2006) Protein repair in the brain, proteomic analysis of endogenous substrates for protein L-isoaspartyl methyltransferase in mouse brain, J. Biol. Chem., 281, 33802–33813.

85. Morrison, G.J., Ganesan, R., Qin, Z., and Aswad, D.W. (2012) Considerations in the identification of endogenous substrates for protein L-isoaspartyl methyltransferase: the case of synuclein, PLoS One, 7, e43288.

86. Biterge, B., Richter, F., Mittler, G., and Schneider, R. (2014) Methylation of histone H4 at aspartate 24 by protein L-isoaspartate O-methyltransferase (PCMT1) links histone modifications with protein homeostasis, Sci. Rep., 4, 66–74.

87. Johnson, B.A., Langmack, E.L., and Aswad, D.W. (1987) Partial repair of deamidation-damaged calmodulin by protein carboxyl methyltransferase, J. Biol.Chem., 262, 12283–12287.

88. Bidinosti, M., Martineau, Y., Frank, F., and Sonenberg, N. (2010) Repair of isoaspartate formation modulates the interaction of deamidated 4E-BP2 with mTORC1 in brain, J. Biol. Chem., 285, 19402–19408.

89. Lee, J.C., Kang, S.U., Jeon, Y., Park, J.W., You, J.S., Ha, S.W., and Han, J.W. (2012) Protein L-isoaspartyl methyltransferase regulates p53 activity, Nat. Commun., 3, 927.

90. Nayak, N.R., Putnam, A.A., Addepalli, B., Lowenson, J.D., Chen, T., Jankowsky, E., and Downie, A.B. (2013) An Arabidopsis ATP-dependent, DEAD-box RNA helicase loses activity upon isoAsp formation but is restored by protein isoaspartyl methyltransferases, Plant Cell, 25, 2573–2586.

91. Adav, S.S., Qian, J., Ang, Y.L., Kalaria, R.N., Lai, M.K., Chen, C.P., and Sze, S.K. (2014) iTRAQ quantitative clinical proteomics revealed role of Na+K+-ATPase and its correlation with deamidation in vascular dementia, J. Proteome Res., 11, 4635–4646.

92. Bierczynska-Krzysik, A., Lopaciuk, M., Pawlak-Morka, R., and Stadnik, D. (2014) Investigation of asparagine deamidation in a SOD1-based biosynthetic human insulin precursor by MALDI-TOF mass spectrometry, Acta Biochim. Pol., 61, 349–357.

93. Dung, T.T.M., Yi, Y.S., Heo, J., Yang, W.S., Kim, J.H., Kim, H.G., Park, J.G., Yo, B.C., Cho, J.Y., and Hong, S. (2016) Critical role of protein L-isoaspartyl methyltransferase in basic fibroblast growth factor-mediated neuronal cell differentiation, BMB Rep., 49, 437–442.

94. Ouanouki, A., and Desrosiers, R.R. (2016) The enzyme L-isoaspartyl (D-aspartyl) methyltransferase is required for VEGF-dependent endothelial cell migration and tubulogenesis, Mol. Cell. Biochem., 413, 37–46.

95. Ouazia, D., Levros, L.C., Jr, Rassart, E., and Desrosiers, R.R. (2015) The protein L-isoaspartyl (D-aspartyl) methyltransferase protects against dopamine-induced apoptosis in neuroblastoma SH-SY5Y cells, Neuroscience, 295, 139–150.

96. Dong, L., Li, Y., Xue, D., and Liu, Y. (2018) PCMT1 is an unfavorable predictor and functions as an oncogene in bladder cancer, IUBMB Life, 70, 291–299.

97. Curnis, F., Longhi, R., Crippa, L., Cattaneo, A., Dondossola, E., Bachi, A., and Corti, A. (2006) Spontaneous formation of L-isoaspartate and gain of function in fibronectin, J. Biol. Chem., 281, 36466–36476.

98. Klionsky, D.J. (2008) Autophagy revisited: a conversation with Christian de Duve, Autophagy, 4, 740–743.

99. Gomez, T.A., Banfield, K.L., Trogler, D.M., and Clarke, S.G. (2007) The L-isoaspartyl-O-methyltransferase in Caenorhabditis elegans larval longevity and autophagy, Dev. Biol., 303, 493–500.

100. Furuchi, T., Sakurako, K., Katane, M., Sekine, M., and Homma, H. (2010) The role of protein L-isoaspartyl/D-aspartyl O-methyltransferase (PIMT) in intracellular signal transduction, Chem. Biodivers., 71, 1337–1348.

101. Krissinel, E., and Henrick, K. (2004) Secondary structure matching (SSM), a new tool for fast protein structure alignment in three dimensions, Acta Crystallogr. D Biol. Crystallogr., 60, 2256–2268.