Biochemistry (Moscow)

, Volume 79, Issue 5, pp 406–416 | Cite as

The role of cytochrome b 5 structural domains in interaction with cytochromes P450

  • G. V. SergeevEmail author
  • A. A. Gilep
  • S. A. Usanov


To understand the role of the structural elements of cytochrome b 5 in its interaction with cytochrome P450 and the catalysis performed by this heme protein, we carried out comparative structural and functional analysis of the two major mammalian forms of membrane-bound cytochrome b 5 — microsomal and mitochondrial, designed chimeric forms of the heme proteins in which the hydrophilic domain of one heme protein is replaced by the hydrophilic domain of another one, and investigated the effect of the highly purified native and chimeric heme proteins on the enzymatic activity of recombinant cytochromes P4503A4 and P45017A1 (CYP3A4 and CYP17A1). We show that the presence of a hydrophobic domain in the structure of cytochrome b 5 is necessary for its effective interaction with its redox partners, while the nature of the hydrophobic domain has no significant effect on the ability of cytochrome b 5 to stimulate the activity of cytochrome P450-catalyzed reactions. Thus, the functional properties of cytochrome b 5 are mainly determined by the structure of the hemebinding domain.

Key words

microsomal cytochrome b5 outer mitochondrial membrane cytochrome b5 cytochrome P450 CYP3A4 CYP17A1 


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  1. 1.
    Giordano, S. J., and Steggles, A. W. (1993) Biochim. Biophys. Acta, 1172, 95–100.PubMedCrossRefGoogle Scholar
  2. 2.
    Altuve, A., Silchenko, S., Lee, K. H., Kuczera, K., Terzyan, S., Zhang, X., Benson, D. R., and Rivera, M. (2001) Biochemistry, 40, 9469–9483.PubMedCrossRefGoogle Scholar
  3. 3.
    Kuroda, R., Ikenoue, T., Honsho, M., Tsujimoto, S., Mitoma, J. Y., and Ito, A. (1998) J. Biol. Chem., 273, 31097–31102.PubMedCrossRefGoogle Scholar
  4. 4.
    Altuve, A., Wang, L., Benson, D. R., and Rivera, M. (2004) Biochem. Biophys. Res. Commun., 314, 602–609.PubMedCrossRefGoogle Scholar
  5. 5.
    Enoch, H. G., Fleming, P. J., and Strittmatter, P. (1979) J. Biol. Chem., 254, 6483–6488.PubMedGoogle Scholar
  6. 6.
    Keyes, S. R., Alfano, J. A., Jansson, I., and Cinti, D. L. (1979) J. Biol. Chem., 254, 7778–7784.PubMedGoogle Scholar
  7. 7.
    Paltuaf, F., Prough, R. A., Masters, B. S., and Johnston, J. M. (1974) J. Biol. Chem., 249, 2661–2662.PubMedGoogle Scholar
  8. 8.
    Fukushima, H., Grinstead, G. F., and Gaylor, J. L. (1981) J. Biol. Chem., 256, 4822–4826.PubMedGoogle Scholar
  9. 9.
    Gacon, G., Lostanlen, D., Labie, D., and Kaplan, J. C. (1980) Proc. Natl. Acad. Sci. USA, 77, 1917–1921.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Livingston, D. J., McLachlan, S. J., La Mar, G. N., and Brown, W. D. (1985) J. Biol. Chem., 260, 15699–15707.PubMedGoogle Scholar
  11. 11.
    Strittmatter, P., Spatz, L., Corcoran, D., Rogers, M. J., Setlow, B., and Redline, R. (1974) Proc. Natl. Acad. Sci. USA, 71, 4565–4569.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Guryev, O. L., Gilep, A. A., Usanov, S. A., and Estabrook, R. W. (2001) Biochemistry, 40, 5018–5031.PubMedCrossRefGoogle Scholar
  13. 13.
    Honsho, M., Mitoma, J. Y., and Ito, A. (1998) J. Biol. Chem., 273, 20860–20866.PubMedCrossRefGoogle Scholar
  14. 14.
    Borgese, N., Gazzoni, I., Barberi, M., Colombo, S., and Pedrazzini, E. (2001) Mol. Biol. Cell, 12, 2482–2496.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Ito, A. (1980) J. Biochem., 87, 73–80.PubMedGoogle Scholar
  16. 16.
    Enoch, H. G., and Strittmatter, P. (1979) J. Biol. Chem., 254, 8976–8981.PubMedGoogle Scholar
  17. 17.
    Gilep, A. A., Guryev, O. L., Shet, M., Fisher, C., Usanov, S. A., and Estabrook, R. (1999) Mol. Steroidogenesis, 29, 85–86.Google Scholar
  18. 18.
    Chudaev, M. V., Gilep, A. A., and Usanov, S. A. (2001) Biochemistry (Moscow), 66, 667–681.CrossRefGoogle Scholar
  19. 19.
    Sergeev, G. V., Gilep, A. A., Estabrook, R. W., and Usanov, S. A. (2006) Biochemistry (Moscow), 71, 790–799.CrossRefGoogle Scholar
  20. 20.
    Sergeev, G. V., Gilep, A. A., Usanov, S. A., and Vasilevskaya, A. V. (2010) Trudy BGU. Mol. Biol., 5, 179–184.Google Scholar
  21. 21.
    Shen, A. L., Porter, T. D., Wilson, T. E., and Kasper, C. B. (1989) J. Biol. Chem., 264, 7584–7589.PubMedGoogle Scholar
  22. 22.
    Laemmli, U. K. (1970) Nature, 227, 680–685.PubMedCrossRefGoogle Scholar
  23. 23.
    Chudaev, M. V., and Usanov, S. A. (1997) Biochemistry (Moscow), 62, 401–411.Google Scholar
  24. 24.
    Harlow, G. R., and Halpert, J. R. (1997) J. Biol. Chem., 272, 5396–5402.PubMedCrossRefGoogle Scholar
  25. 25.
    Chung, B. C., Picado-Leonard, J., Haniu, M., Bienkowski, M., Hall, P. F., Shively, J. E., and Miller, W. L. (1987) Proc. Natl. Acad. Sci. USA, 84, 407–411.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Grigoryev, D. N., Kato, K., Njar, V. C., Long, B. J., Ling, Y. Z., Wang, X., Mohler, J., and Brodie, A. M. (1999) Anal. Biochem., 267, 319–330.PubMedCrossRefGoogle Scholar
  27. 27.
    Soucy, P., and Luu-The, V. (2002) J. Steroid Biochem. Mol. Biol., 80, 71–75.PubMedCrossRefGoogle Scholar
  28. 28.
    Perret, A., and Pompon, D. (1998) Biochemistry, 37, 11412–11424.PubMedCrossRefGoogle Scholar
  29. 29.
    Schenkman, J. B., Voznesensky, A. I., and Jansson, I. (1994) Arch. Biochem. Biophys., 314, 234–241.PubMedCrossRefGoogle Scholar
  30. 30.
    Yamazaki, H., Johnson, W. W., Ueng, Y. F., Shimada, T., and Guengerich, F. P. (1996) J. Biol. Chem., 271, 27438–27444.PubMedCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2014

Authors and Affiliations

  1. 1.Institute of Bioorganic ChemistryAcademy of Sciences of BelarusMinskBelarus

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