Biochemistry (Moscow)

, Volume 70, Issue 8, pp 908–912 | Cite as

Inhibition of Family II Pyrophosphatases by Analogs of Pyrophosphate and Phosphate

  • A. B. Zyryanov
  • R. Lahti
  • A. A. Baykov


Imidodiphosphate (the pyrophosphate analog containing a nitrogen atom in the bridge position instead of oxygen) is a potent inhibitor of family II pyrophosphatases from Streptococcus mutans and Streptococcus gordonii (inhibition constant Ki ≈ 10 µM), which is slowly hydrolyzed by these enzymes with a catalytic constant of ≈1 min−1. Diphosphonates with different substituents at the bridge carbon atom are much less effective (Ki = 1–6 mM). The value of Ki for sulfate (a phosphate analog) is only 12 mM. The inhibitory effect of the pyrophosphate analogs exhibits only a weak dependence on the nature of the metal ion (Mn, Mg, or Co) bound in the active site.

Key words

pyrophosphatase diphosphonate phosphate inhibition family II Streptococcus mutans Streptococcus gordonii 


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  1. 1.
    Young, T. W., Kuhn, N. J., Wadeson, A., Ward, S., Burges, D., and Cook, J. D. (1988) Microbiology, 144, 2563–2571.Google Scholar
  2. 2.
    Shintani, T., Uchiumi, T., Yonezava, T., Salminen, A., Baykov, A. A., Lahti, R., and Hachimori, A. (1988) FEBS Lett., 439, 263–266.CrossRefGoogle Scholar
  3. 3.
    Zyryanov, A. B., Shestakov, A. S., Lahti, R., and Baykov, A. A. (2002) Biochem. J., 367, 901–906.CrossRefPubMedGoogle Scholar
  4. 4.
    Kuhn, N., Wadeson, A., Ward, S., and Young, T. W. (2000) Arch. Biochem. Biophys., 379, 292–298.CrossRefPubMedGoogle Scholar
  5. 5.
    Parfenyev, A. N., Salminen, A., Halonen, P., Hachimori, A., Baykov, A. A., and Lahti, R. (2001) J. Biol. Chem., 276, 24511–24518.CrossRefPubMedGoogle Scholar
  6. 6.
    Merckel, M. C., Fabrichniy, I. P., Salminen, A., Kalkkinen, N., Baykov, A. A., Lahti, R., and Goldman, A. (2001) Structure, 9, 289–297.CrossRefPubMedGoogle Scholar
  7. 7.
    Ahn, S., Milner, A. J., Futterer, K., Konopka, M., Ilias, M., Young, T. W., and White, S. A. (2001) J. Mol. Biol., 313, 797–811.CrossRefPubMedGoogle Scholar
  8. 8.
    Zyryanov, A. B., Vener, A. V., Salminen, A., Goldman, A., Lahti, R., and Baykov, A. A. (2004) Biochemistry, 43, 1065–1074.CrossRefPubMedGoogle Scholar
  9. 9.
    Charney, J., Fisher, W. P., and Hegarty, C. P. (1951) J. Bacteriol., 62, 145–148.PubMedGoogle Scholar
  10. 10.
    Martin, M. E., Byers, B. R., Olson, M. O. J., Salin, M. L., Arceneaux, J. E. L., and Tolbert, C. (1986) J. Biol. Chem., 261, 9361–9367.PubMedGoogle Scholar
  11. 11.
    Larsen, M., Willett, R., and Yount, R. G. (1969) Science, 166, 1510–1511.Google Scholar
  12. 12.
    Nielsen, M. L., Ferguson, R. R., and Coacley, W. S. (1961) J. Am. Chem. Soc., 83, 99–104.CrossRefGoogle Scholar
  13. 13.
    Kirsanov, A. V., and Zhmurova, N. N. (1958) Zh. Org. Khim., 28, 2478–2484.Google Scholar
  14. 14.
    Baykov, A. A., and Avaeva, S. M. (1981) Analyt. Biochem., 116, 1–4.CrossRefPubMedGoogle Scholar
  15. 15.
    Smirnova, I. N., Baykov, A. A., and Avaeva, S. M. (1986) FEBS Lett., 206, 121–124.CrossRefPubMedGoogle Scholar
  16. 16.
    Chanley, J. D., and Feageson, E. (1963) J. Am. Chem. Soc., 85, 1181–1190.CrossRefGoogle Scholar
  17. 17.
    Rizkalla, E. N. (1983) Rev. Inorg. Chem., 5, 223–304.Google Scholar
  18. 18.
    Smirnova, I. N., Kudryavtseva, N. A., Komissarenko, S. V., Tarusova, N. B., and Baykov, A. A. (1988) Arch. Biochem. Biophys., 267, 280–284.CrossRefPubMedGoogle Scholar
  19. 19.
    Baykov, A. A., Fabrichniy, I. P., Pohjanjoki, P., Zyryanov, A. B., and Lahti, R. (2000) Biochemistry, 39, 11939–11947.CrossRefPubMedGoogle Scholar
  20. 20.
    Avaeva, S., Kurilova, S., Nazarova, T., Rodina, E., Vorobyeva, N., Sklyankina, V., Grigorjeva, O., Harutyunyan, E., Oganessyan, V., Wilson, K., Dauter, Z., Huber, R., and Mather, T. (1997) FEBS Lett., 410, 502–508.CrossRefPubMedGoogle Scholar

Copyright information

© MAIK “Nauka/Interperiodica” 2005

Authors and Affiliations

  1. 1.Belozersky Institute of Physico-Chemical Biology and Faculty of ChemistryLomonosov Moscow State UniversityMoscowRussia
  2. 2.Department of Biochemistry and Food ChemistryUniversity of TurkuTurkuFinland

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