Advertisement

Biochemistry (Moscow)

, 73:237 | Cite as

Role of A-chain in functioning of the active site of human α-thrombin

  • M. V. Kolodzeiskaya
  • L. I. SokolovskayaEmail author
  • G. L. Volkov
Review

Abstract

This review summarizes current data suggesting that A-chain of the human α-thrombin molecule plays a role of allosteric effector in catalytic reactions with various substrates. Special attention is paid to the relationship between A-chain structure and catalytic activity of thrombin. The existence of this relationship is based on studies of natural mutation of A-chain of the α-thrombin molecule. Use of molecular and essential dynamics confirmed the role of A-chain in changes of conformation and catalytic properties of this enzyme; these changes involve residues located in the specificity sites and some inserting loops. Current knowledge on structure and properties of thrombin can be used for the development of new antithrombin agents.

Key words

thrombin allosterics mutagenesis protein C modulation thrombomodulin molecular dynamics 

Abbreviations

BPTI

basic pancreatic thrombin inhibitor

ED

essential dynamics

MD

molecular dynamics

α-NAPAP

N-α-[2-naphthyl-sulfonyl-glycyl]-4-amidinophenylalanylpiperidine

PAR1

protease-activated receptor 1

PPACK

D-Phe-Pro-Arg-chloromethylketone

References

  1. 1.
    Fenton, J. W. (1991) Blood Coagulat. Fibrinol., 2, 69–75.CrossRefGoogle Scholar
  2. 2.
    Fenton, J. W., and Bing, D. H. (1986) Thromb. Haemost., 12, 200–208.CrossRefGoogle Scholar
  3. 3.
    Kibirev, V. K., and Sereiskaya, A. A. (1989) Biokhim. Zhivotn. Chel., 13, 10–18.Google Scholar
  4. 4.
    Sereiskaya, A. A., Kibirev, V. K., and Serebryanyi, S. B. (1981) Biokhim. Fiziol. Zhivotn. Chel., 5, 3–28.Google Scholar
  5. 5.
    Serebryanyi, S. B. (1982) Biokhim. Zhivotn. Chel., 6, 14–16.Google Scholar
  6. 6.
    Blomback, B., Blomback, M., Olsson, P. L., and Scand, J. (1986) Clin. Ivest., 107, 59–64.Google Scholar
  7. 7.
    March, H. C., Meinwald, J. C., Lee, S., Martinell, R. A., and Scheraga, H. A. (1985) Biochemistry, 24, 2806–2816.CrossRefGoogle Scholar
  8. 8.
    Strukova, S. M., Sereiskaya, A. A., and Osadchuk, T. V. (1989) Usp. Sovr. Biol., 107, 41–53.Google Scholar
  9. 9.
    Gershkovich, A. A. (1996) Biochemistry (Moscow), 61, 817–824.Google Scholar
  10. 10.
    Kibirev, V. K., and Gershkovich, A. A. (1999) Ukr. Biokhim. Zh., 71, 5–26.PubMedGoogle Scholar
  11. 11.
    Rajesh Sinh, R., and Chang, J. Y. (2003) Biochim. Biophys. Acta, 1651, 85–92.Google Scholar
  12. 12.
    Huntington, J. A., and Esmon, C. T. (2003) Structure, 11, 363–364.CrossRefGoogle Scholar
  13. 13.
    Davie, E. W., and Kulman, J. D. (2006) Semin. Thromb. Haemost., 32,Suppl. 1, 3–15.CrossRefGoogle Scholar
  14. 14.
    Bode, W. (2006) Semin. Thromb. Haemost., 32,Suppl. 1, 16–31.CrossRefGoogle Scholar
  15. 15.
    Bode, W. (2006) Blood Cells Mol. Dis., 36, 122–130.PubMedCrossRefGoogle Scholar
  16. 16.
    Bush-Pelc, L. A., Marino, F., Chen, Z., Pineda, A. O., Mathews, F. S., and Di Cera, E. (2007) J. Biol. Chem., 282, 27165–27170.PubMedCrossRefGoogle Scholar
  17. 17.
    Kolodzeiskaya, M. V., and Volkov, G. L. (2006) Ukr. Biokhim. Zh., 78, 22–31.Google Scholar
  18. 18.
    Kolodzeiskaya, M. V., and Volkov, G. L. (2007) Ukr. Biokhim. Zh., 79, 5–21.Google Scholar
  19. 19.
    Stubbs, M. T., and Bode, W. (1993) Thromb. Res., 69, 1–58.PubMedCrossRefGoogle Scholar
  20. 20.
    Neurath, H. (1985) Fed. Proc., 44, 2907–2913.PubMedGoogle Scholar
  21. 21.
    Bode, W., Turk, D., and Karshikov, A. (1992) Protein Sci., 1, 426–430.PubMedCrossRefGoogle Scholar
  22. 22.
    De Cristofaro, R., Akhavan, S., Altomare, C., Carotti, A., Peyvandi, F., and Mannucci, P. M. (2004) J. Biol. Chem., 279, 13035–13043.PubMedCrossRefGoogle Scholar
  23. 23.
    Fischer, B. E., Schlokatm, U., Mittererm, A., Grillbergerm, L., and Reiterm, M. (1996) Protein Eng., 9, 921–926.PubMedCrossRefGoogle Scholar
  24. 24.
    Petrovan, R. J., Govers-Riemslag, J. W., Noua, G., Hemker, H. C., Tans, G., and Rosing, J. (1998) Biochemistry, 37, 1185–1191.PubMedCrossRefGoogle Scholar
  25. 25.
    Hageman, T. C., Endres, G. F., and Scheraga, H. A. (1975) Arch. Biochem. Biophys., 171, 327–336.PubMedCrossRefGoogle Scholar
  26. 26.
    Nemethy, G., and Scheraga, H. A. (1981) Biochem. Biophys. Res. Commun., 98, 482–487.PubMedCrossRefGoogle Scholar
  27. 27.
    Sereiskaya, A. A., Osadchuk, T. V., Kornelyuk, A. I., Serebyanyi, S. B., and Atepalikhina, S. A. (1986) Biokhimiya, 51, 1659–1666.Google Scholar
  28. 28.
    Sereiskaya, A. A., Osadchuk, T. V., Kornelyuk, A. I., and Serebyanyi, S. B. (1989) Biokhimiya, 54, 542–548.Google Scholar
  29. 29.
    Akhavan, S., Mannucci, P. M., Lak, M., Mancuso, G., Mazzucconi, M. G., Rocino, A., Jenkins, P. V., and Perkins, S. J. (2000) Thromb. Haemost., 84, 989–997.PubMedGoogle Scholar
  30. 30.
    Sun, W. Y., Witte, D. P., Degenj, J. L., Colbert, M. C., Burkart, M. C., Hoemback, K., Xiao, Q., Bugge, T. H., and Degen, S. (1998) Proc. Natl. Acad. Sci. USA, 95, 7597–7602.PubMedCrossRefGoogle Scholar
  31. 31.
    Xue, J., Wu, Q., Westfielde, L. A., Tuley, E. A., Lu, D., Zhang, Q., Shim, K., Zheng, X., and Sadler, J. E. (1998) Proc. Natl. Acad. Sci. USA, 95, 7603–7607.PubMedCrossRefGoogle Scholar
  32. 32.
    Lefkowitz, J. B., Haver, T., Clarke, S., Jacobson, L., Willer, A., Nuss, R., Manco-Jonson, M., and Hathaway, W. E. (2000) Br. J. Haematol., 168, 182–187.CrossRefGoogle Scholar
  33. 33.
    Sun, W. Y., Smirnow, D., Jenkins, M. L., and Degen, S. J. (2001) Thromb. Haemost., 85, 651–654.PubMedGoogle Scholar
  34. 34.
    Akhavan, S., Luciani, M., Lavoretano, S., and Mannucci, P. M. (2003) Br. J. Haematol., 120, 142–144.PubMedCrossRefGoogle Scholar
  35. 35.
    Ortiz, J., Lefkowitz, J. B., Weller, A., and Santiago-Bornero, P. (2002) Haemophilia, 8, 836–839.CrossRefGoogle Scholar
  36. 36.
    Akhavan, S., de Cristofaro, R., Peyvandi, F., Lavoretano, S., Landolfi, R., and Mannucci, P. M. (2002) Blood, 100, 1347–1353.PubMedCrossRefGoogle Scholar
  37. 37.
    Di Cera, E., Guinto, E. R., Vindigni, A., Dang, Q. D., Ayala, G. M., Wuyi, M., and Tulinsky, A. (1995) J. Biol. Chem., 270, 22089–22092.PubMedCrossRefGoogle Scholar
  38. 38.
    De Filippis, V., Colombo, G., Russo, I., Spadari, B., and Fontana, A. (2002) Biochemistry, 41, 13556–13569.PubMedCrossRefGoogle Scholar
  39. 39.
    Hess, B., Bekker, H., Fraaije, Je, J., and Beredsen, H. J. C. (1997) J. Comput. Chem., 18, 1463–1472.CrossRefGoogle Scholar
  40. 40.
    Huntington, J. A., and Esmon, C. T. (2003) Structure, 11, 469–479.PubMedCrossRefGoogle Scholar
  41. 41.
    Abrahams, J. P., and Thomassen, E. A. (2003) Structure, 11, 363–364.PubMedCrossRefGoogle Scholar
  42. 42.
    Dahlback, B., and Villoutreix, B. O. (2005) FEBS Lett., 579, 3310–3316.PubMedCrossRefGoogle Scholar
  43. 43.
    Stone, S. R., Esmon, C. T., and Stubbs, M. T. (1997) EMBO J., 16, 2997–2984.Google Scholar
  44. 44.
    Marquart, M., Walter, J., Deisenhofer, J., Bode, W., and Huber, R. (1963) Acta Crystallogr. Sec. B, 39, 480–490.Google Scholar
  45. 45.
    Burgi, H. B., Dunitz, J. D., and Shefter, E. (1973) J. Am. Chem. Soc., 95, 5065–5067.CrossRefGoogle Scholar
  46. 46.
    Suel, G. M., Lockless, S. W., Wall, M. A., and Ranganathan, R. (2003) Nature Struct. Biol., 10, 59–68.PubMedCrossRefGoogle Scholar
  47. 47.
    Dennis, M. S., Eigenbrot, C., Skelton, N. J., Ultsch, M. H., Santell, L., Dwyer, M. D., O’Connel, M. P., and Lasarus, R. A. (2000) Nature, 404, 465–470.PubMedCrossRefGoogle Scholar
  48. 48.
    De Cristofaro, R., Corotti, A., Akhavan, S., Palla, R., Peyvandi, F., Altomare, C., and Mannucci, P. M. (2006) FEBS J., 273, 159–169.PubMedCrossRefGoogle Scholar
  49. 49.
    Di Cera, E., de Cristofaro, R., Albright, D. J., and Fenton, J. W. (1991) Biochemistry, 30, 7913–7924.PubMedCrossRefGoogle Scholar
  50. 50.
    De Cristofaro, R., and di Cera, E. (1990) J. Mol. Biol., 216, 1077–1086.PubMedCrossRefGoogle Scholar
  51. 51.
    Stone, S. R., Betz, A., and Hofsteenge, J. (1991) Biochemistry, 30, 9841–9848.PubMedCrossRefGoogle Scholar
  52. 52.
    Enyedy, E. J., and Kovach, J. M. (2004) J. Am. Chem. Soc., 126, 6017–6024.PubMedCrossRefGoogle Scholar
  53. 53.
    Wells, C. M., and di Cera, E. (1992) Biochemistry, 31, 11721–11730.PubMedCrossRefGoogle Scholar
  54. 54.
    Amadei, A., Linssen, A. B., and Berendsen, H. J. (1993) Proteins Struct. Funct. Genet., 17, 412–425.PubMedCrossRefGoogle Scholar
  55. 55.
    Bell, R., Willem, K., Stevens, W. K., Jia, Z., Samis, J., Cote, H. C. F., Mac Gillivray, R. T. A., and Nesheim, M. E. (2000) J. Biol. Chem., 275, 29513–29520.PubMedCrossRefGoogle Scholar
  56. 56.
    Edison, A. S., Abildgaard, F., Westler, W. M., Mooberry, E. S., Woody, R. W., and Dunker, A. K. (1996) in Circular Dichroism and the Conformational Analysis of Biomolecules (Fasman, G. D., ed.) Plenum Press, N. Y., pp. 136–144.Google Scholar
  57. 57.
    Arosio, D., Ayla, Y. M., and di Cera, E. (2000) Biochemistry, 39, 8095–8101.PubMedCrossRefGoogle Scholar
  58. 58.
    De Filippis, V., de Dea, E., Lucatello, F., and Frasson, R. (2005) Biochem. J., 390, 485–492.PubMedCrossRefGoogle Scholar
  59. 59.
    Singh, R. R., and Cheng, J. Y. (2003) Biochim. Biophys. Acta, 1651, 85–92.Google Scholar
  60. 60.
    Mecozzi, S., West, A. P., and Dougherty, D. A. (1996) Proc. Natl. Acad. Sci. USA, 20, 10566–10571.CrossRefGoogle Scholar
  61. 61.
    Daugherty, D. A. (1996) Science, 271, 163–186.CrossRefGoogle Scholar
  62. 62.
    Doolittle, R. F., Feng, D. F., Tsang, S., Cho, G., and Littie, E. (1996) Science, 271, 470–477.PubMedCrossRefGoogle Scholar
  63. 63.
    De Filippis, V., Quarzago, D., Vindigni, A., di Cera, E., and Fontana, A. (1998) Biochemistry, 37, 13507–13515.PubMedCrossRefGoogle Scholar
  64. 64.
    De Filippis, V., Russo, I., Vindigni, A., di Cera, E., Salmaso, S., and Fontana, A. (1999) Protein Sci., 8, 2213–2217.PubMedCrossRefGoogle Scholar
  65. 65.
    Kim, K. S., Tarakeshuwar, P., and Lee, J. G. (2000) Chem. Rev., 100, 4145–4185.PubMedCrossRefGoogle Scholar
  66. 66.
    Di Cera, E. (2003) Chest, 124, 11–17.CrossRefGoogle Scholar
  67. 67.
    Krem, M. M., and di Cera, E. (2001) EMBO J., 20, 3036–3045.PubMedCrossRefGoogle Scholar
  68. 68.
    Krem, M. M., and di Cera, E. (2002) Trends Biochem. Sci., 27, 67–74.PubMedCrossRefGoogle Scholar
  69. 69.
    Pineda, A. O., Savvides, S. N., Waksman, G., and di Cera, E. (2002) J. Biol. Chem., 277, 40177–40180.PubMedCrossRefGoogle Scholar
  70. 70.
    Prasad, S., Wright, K. J., Banerjee Roy, D., Bush, L. A., Cantwell, A. M., and di Cera, E. (2003) Proc. Natl. Acad. Sci. USA, 100, 13785–13790.PubMedCrossRefGoogle Scholar
  71. 71.
    Kurganov, B. I. (1978) Allosteric Enzymes [in Russian], Nauka, Moscow.Google Scholar
  72. 72.
    Bode, W., Mayr, I., Baumann, U., Huber, R., Stone, S. R., and Hofsteene, J. (1989) EMBO J., 8, 3467–3475.PubMedGoogle Scholar
  73. 73.
    Gruber, A., Cantwell, A. M., di Cera, E., and Manson, S. R. (2002) J. Biol. Chem., 277, 27581–27584.PubMedCrossRefGoogle Scholar
  74. 74.
    Pineda, A. O., Carrel, Ch. J., Bush, L. A., and Prasad, S. (2004) J. Biol. Chem., 279, 31842–31853.PubMedCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2008

Authors and Affiliations

  • M. V. Kolodzeiskaya
    • 1
  • L. I. Sokolovskaya
    • 1
    Email author
  • G. L. Volkov
    • 1
  1. 1.Palladin Institute of BiochemistryNational Academy of Sciences of UkraineKievUkraine

Personalised recommendations