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Structure-function relations in flavodoxins

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Summary

Flavodoxins are low molecular weight, FMN containing, proteins which function as electron transfer agents in a variety of microbial metabolic processes, including nitrogen fixation. Utilizing structural information obtained from x-ray crystal analysis, it has been possible to derive some new and important insights into the relationships which exist between flavin properties and protein environment by comparing the spectroscopic, thermodynamic and kinetic behavior of the flavodoxins with that of free flavin. Thus, for example, a qualitative understanding of the contribution of the protein to flavin redox potentials, semiquinone reactivity and mechanism of electron transfer is beginning to emerge. The highly negative redox potential required for the biochemical activity of the flavodoxins is accomplished by stabilizing the semiquinone via a hydrogen bond to the N-5 position of the flavin and destabilizing the fully-reduced form by constraining it to assume an unfavorable planar conformation. The reactivity of the semiquinone form is lowered by the aforementioned hydrogen bond, as well as by an interaction with a tryptophan residue in the binding site. Electron transfer is accomplished through the exposed dimethylbenzene ring of the bound coenzyme. Although it is not possible at present to determine the extent to which this understanding can be generalized to other flavoproteins, it is clear that a study of the flavodoxins will provide us with at least some of the principles which biological systems have used to modify flavin properties to fulfill a biochemical need.

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References

  1. Knight, E. Jr. & Hardy, R. W. F., 1966. J. Biol. Chem. 241, 2752–2756.

    Google Scholar 

  2. Hinkson, J. W. & Bulen, W. A., 1967. J. Biol. Chem. 242, 3345–3351.

    Google Scholar 

  3. Mayhew, S. G. & Ludwig, M. L. 1975. Enzymes 12B, 57–118.

    Google Scholar 

  4. Yoch, D. C. & Valentine, R. C. 1972. Ann. Rev. Microbiol. 26, 139–162.

    Google Scholar 

  5. Uyeda, K. & Rabinowitz, J. C. 1971. J. Biol. Chem. 246, 3111–3119.

    Google Scholar 

  6. Valentine, R. C., Jackson, R. C., & Wolfe, R. S. 1962. Biochem. Biophys. Res. Commun. 7, 453–456.

    Google Scholar 

  7. Fredericks, W. W. & Stadtman, E. R. 1965. J. Biol. Chem. 240, 4065–4071.

    Google Scholar 

  8. Jungermann, K., Rupprecht, E., Ohrloff, C., Thauer, R. K. and Decker, K. 1971. J. Biol. Chem. 246, 960–963.

    Google Scholar 

  9. Thauer, R. K., Rupprecht, E., Ohrloff, C., Jungermann, K. and Decker, K. 1971. J. Biol. Chem. 246, 954–959.

    Google Scholar 

  10. Hatchikian, E. C., LeGall, J., Bruschi, M. and Dubourdieu, M. 1972. Biochim. Biophys. Acta. 258, 701–708.

    Google Scholar 

  11. Orme-Johnson, W. H., Davis, L. C., Henzl, M. T., Averill, B. A., Orme-Johnson, N. R., Munck, E. & Zimmerman, R. 1977. In: Recent Developments in Nitrogen Fixation (Newton, W., Postgate, J. R. and Rodriguez-Barrueco, C. eds.) pp. 271–285, Academic Press, New York.

  12. D'Eustachio, A. J. & Hardy, R. W. F. 1964. Biochem. Biophys. Res. Common. 15, 319–323.

    Google Scholar 

  13. Mortenson, L. E. 1964. Biochim. Biophys. Acta. 81, 473–478.

    Google Scholar 

  14. Benemann, J. R., Yoch, D. C., Valentine, R. C. & Arnon, D. I. 1969. Proc. Nat. Acad. Sci. USA. 64, 1079–1086.

    Google Scholar 

  15. Yoch, D. C., Benemann, J. R., Valentine, R. C., & Arnon, D. I. 1969. Proc. Nat. Acad. Sci. USA. 64, 1404–1410.

    Google Scholar 

  16. Scherings, G., Haaker, H. & Veeger, C. 1977. Eur. J. Biochem. 77, 621–630.

    Google Scholar 

  17. Haaker, H. & Veeger, C. 1977. Eur. J. Biochem. 77, 1–10.

    Google Scholar 

  18. Smillie, R. M. 1965. Biochem. Biophys. Res. Commun. 20, 621–629.

    Google Scholar 

  19. Tollin, G. & Edmondson, D. E. 1980. Meth. Enzymol. 69, 392–405.

    Google Scholar 

  20. Cusanovich, M. A. & Edmondson, D. E. 1971. Biochem. Biophys. Res. Common. 45, 327–336.

    Google Scholar 

  21. Mayhew, S. G. 1971. Biochim. Biophys. Acta. 235, 276–288.

    Google Scholar 

  22. Yoch, D. C. 1975. Arch. Biochem. Biophys. 170, 326–333.

    Google Scholar 

  23. Tanaka, M., Haniu, M., Yasunobu, K. T., & Mayhew, S. G. 1974. J. Biol. Chem. 249, 4393–4396.

    Google Scholar 

  24. Dubourdieu, M. and Fox, J. L. 1977. J. Biol. Chem., 252, 1453–1463.

    Google Scholar 

  25. Tanaka, M., Haniu, M., Yasunobu, K. T., Mayhew, S. G., and Massey, V. 1974. J. Biol. Chem., 249, 4397.

    Google Scholar 

  26. Tanaka, M., Haniu, M., Yasunobu, K. T., and Yoch, D. C. 1977. Biochemistry, 16, 3525–3537.

    Google Scholar 

  27. MacKnight, M. L., Gray, W. R., and Tollin, G. 1974. Biochem. Biophys. Res. Commun., 59, 630–637.

    Google Scholar 

  28. Fox, J. L., 1976. In: Protein Structure and Evolution (Fox, J. L., Deyl, Z., & Blazej, A., editors). pp. 261–272, Marcel Dekker Inc., New York.

  29. Edmondson, D. E. & Tollin, G. 1971. Biochemistry, 10, 113–124.

    Google Scholar 

  30. D'Anna, J. A. & Tollin, G. 1972. Biochemistry, 11, 1073–1080.

    Google Scholar 

  31. Edmondson, D. E. & Tollin, G. 1971. Biochemistry 10, 124–132.

    Google Scholar 

  32. Barman, B. G. & Tollin, G. 1972. Biochemistry 11, 4746–4754.

    Google Scholar 

  33. Mayhew, S. G. 1971. Biochim. Biophys. Acta. 235, 289–302.

    Google Scholar 

  34. Ghisla, S., Massey, V., Lhoste, J. M. & Mayhew, S. G. 1974. Biochemistry 13, 589–597.

    Google Scholar 

  35. Hyde, J. S., Eriksson, L. E. G. & Ehrenberg, A. 1970. Biochim. Biophys. Acta. 222, 688–692.

    Google Scholar 

  36. Palmer, G., Muller, F. & Massey, V. 1971. In: Flavins and Flavoproteins (Kamin, H., ed). pp. 123–140, University Park Press, Maryland.

  37. MacDonald, C. C. & Phillips, W. D. 1971. In: Fine Structure of Proteins and Nuclei Acids (Fasman, G. D. & Timasheff, S. N., eds.) pp. 1–48. Dekker, New York.

  38. Crespi, H. L., Norris, J. R., Bays, J. P. & Katz, J. J. 1973. Ann. N.Y. Acad. Sci. 222, 800–815.

    Google Scholar 

  39. Fritz, J., Müller, F. & Mayhew, S. G. 1973. Helv. Chim. Acta. 56, 2250–2254.

    Google Scholar 

  40. Crespi, H. L., Norris, J. R. & Katz, J. J. 1972. Nature New Biol. 236, 178–180.

    Google Scholar 

  41. James, T. L., Ludwig, M. L. & Cohn, M. 1973. Proc. Nat. Acad. Sci. USA. 70, 3292–3295.

    Google Scholar 

  42. Eriksson, L. E. G., & Ehrenberg, A. 1973. Biochim. Biophys. Acta. 293, 57–66.

    Google Scholar 

  43. Burnett, R. M., Darling, G. D., Kendall, D. S., LeQuesne, M. E., Mayhew, S. G., Smith, W. W., & Ludwig, M. L. 1974. J. Biol. Chem. 249, 4383–4392.

    Google Scholar 

  44. Smith, W. W., Burnett, R. M., Darling, G. D., & Ludwig, M. L. 1977. J. Mol. Biol. 117, 195–225.

    Google Scholar 

  45. Ludwig, M. L., Burnett, R, M., Darling, G. D., Jordan, S. R., Kendall, D. S., & Smith, W. W. 1975. In: Structure and Conformation of Nucleic Acids and Protein-Nucleic Acid Interactions. (Sundaralingam, M. and Rao, S. T., editors) pp. 407–429, University Park Press, Baltimore.

  46. Ludwig, M. L., Burnett, R. M., Darling, G. D., Jordan, S. R., Kendall, D. S., & Smith, W. W., 1976. Flavins and Flavoproteins (Singer, T. P, editor). pp. 393–403, Elsevier Scientific Publishing Co., Amsterdam.

  47. Rao, S. T., and Rossmann, M. G., 1973. J. Mol. Biol., 76, 241–256.

    Google Scholar 

  48. Shiga, K., and Tollin G., 1976. In: Flavins and Flavoproteins, (Singer, T. P., editor). pp. 422–433, Elsevier Scientific Publishing Co., Amsterdam.

  49. Draper, D. and Ingraham, L. L. 1968. Arch. Biochem. Biophys. 125, 802–808.

    Google Scholar 

  50. Gillard, J. M., and Tollin G., 1974. Biochem. Biophys. Res. Commun. 58, 328–336.

    Google Scholar 

  51. Kierkegaard, P., Norrestam, R., Werner, P., Csöregh, I. Von Glehn, M., Karlsson, R., Leyonmarck, M., Rönnquist, O., Stensland, B., Tillberg, O., & Torbjörnsson, 1971, Flavins and Flavoproteins, (Kamin, H. editor). pp. 1–22, University Park Press, Baltimore.

  52. Faraggi, M., and Klapper, M. H., 1979. J. Biol. Chem., 254, 8139–8142.

    Google Scholar 

  53. Dubourdieu, M., MacKnight, M. L., and Tollin, G., 1974. Biochem. Biophys. Res. Commun. 60, 649–655.

    Google Scholar 

  54. Watenpaugh, K. D., Sieker, L. C., Jensen, L. H., LeGall, J. and Dubourdieu, M. 1972, Proc. Nat. Acad. Sci. USA. 69, 3185–3188.

    Google Scholar 

  55. Watenpaugh, K. D., Sieker, L. C., and Jensen, L. H., 1973. Proc. Nat. Acad. Sci. USA. 70, 3857–3860.

    Google Scholar 

  56. Watenpaugh, K. D., Sieker, L. C., and Jensen, L. H. 1976. In Flavins and Flavoproteins, (Singer, T. P. editor) pp. 405–410, Elsevier Scientific Publishing Co., Amsterdam.

  57. Dubourdieu, M., LeGall, J., & Favaudon, V. 1975. Biochim. Biophys. Acta, 376, 519–532.

    Google Scholar 

  58. D'Anna, J. A. & Tollin, G. 1971. Biochemistry 10, 57–64.

    Google Scholar 

  59. Ryan, J. & Tollin, G. 1973 Biochemistry 12, 4550–4554.

    Google Scholar 

  60. Andrews, L. J., MacKnight, M. L., Ryan, J. & Tollin, G. 1973. Biochem. Biophys. Res. Commun. 55, 1165–1172.

    Google Scholar 

  61. MacKnight, M. L., Gillard, J. M. & Tollin, G. 1973. Biochemistry 12, 4200–4206.

    Google Scholar 

  62. Edmondson, D. E. & James, T. C. 1979. Proc. Nat. Acad. Sci. USA. 76, 3786–3789.

    Google Scholar 

  63. Jung, J. and Tollin, G., submitted for publication.

  64. Edmondson, D. E., and Tollin, G. 1971. Biochemistry 10, 133–145.

    Google Scholar 

  65. Mayhew, S. G., Foust, G. P. and Massey, V., 1969. J. Biol. Chem. 244, 803–810.

    Google Scholar 

  66. Mayhew, S. G., 1978. Eur. J. Biochem. 85, 535–547.

    Google Scholar 

  67. Mayhew, S. G. & Massey, V., 1973. Biochim. Biophys. Acta. 315, 181–190.

    Google Scholar 

  68. Vaish, S. P. & Tollin, G. 1971. J. Bioenergetics 2, 61–72.

    Google Scholar 

  69. Massey, V., Stanhovich, M., and Hemmerich, P., 1978. Biochemistry, 17, 1–8.

    Google Scholar 

  70. Massey, V. and Hemmerich, P. 1978. Biochemistry 17, 9–17.

    Google Scholar 

  71. Barman, B. G., & Tollin, G. 1972. Biochemistry 11, 4760–4765.

    Google Scholar 

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  1. Department of Biochemistry, University of Arizona, 85721, Tucson, Arizona, USA

    Royce P. Simondsen & Gordon Tollin

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  1. Royce P. Simondsen
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Simondsen, R.P., Tollin, G. Structure-function relations in flavodoxins. Mol Cell Biochem 33, 13–24 (1980). https://doi.org/10.1007/BF00224568

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  • DOI: https://doi.org/10.1007/BF00224568

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