Molecular Dynamics Study of Thymidine Phosphorylase from E. coli in the Apo Form and in Complexes with Substrates


Models of E. coli thymidine phosphorylase in complexes with the substrates — the complex with phosphate and the complex with phosphate and thymidine — were obtained by molecular docking calculations. The influence of the substrates on domain movements in the dimeric thymidine phosphorylase molecule was probed by molecular dynamics simulations. The two subunits were shown to function asynchronously. In the thymidine phosphorylase/phosphate and thymidine phosphorylase/phosphate/thymidine complexes, phosphate is more weakly bound in the active site and moves away from the phosphate-binding site during the 60-ns trajectory, whereas thymidine remains in the active site but undergoes conformational changes.

This is a preview of subscription content, log in to check access.

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.
Fig. 6.


  1. 1

    M. J. Pugmire and S. E. Ealick, Biochem. J. 361, 1 (2002).

    Article  Google Scholar 

  2. 2

    M. Ligo, K. Nishikata, Y. Nakajiama, et al., Biochem. Pharmacol. 39 (7), 1247 (1990).

    Article  Google Scholar 

  3. 3

    A. Yoshimura, Y. Kuwazuru, T. Furukawa, et al., Biochim. Biophys. Acta 1034, 107 (1990).

    Article  Google Scholar 

  4. 4

    K. Usuki, J. Saras, J. Waltenberger, et al., Biochem. Biophys. Res. Commun. 184, 1311 (1992).

    Article  Google Scholar 

  5. 5

    S. Akiyama, T. Furukawa, T. Sumizawa, et al., Cancer Sci. 95 (11), 851 (2004).

    Article  Google Scholar 

  6. 6

    E. L. Schwartz, N. Baptiste, S. Megati, et al., Cancer Res. 55, 3543 (1995).

    Google Scholar 

  7. 7

    M. R. Walter, W. J. Cook, L. B. Cole, et al., J. Biol. Chem. 265, 14016 (1990).

    Google Scholar 

  8. 8

    M. J. Pugmire, W. J. Cook, A. Jasanoff, et al., J. Mol. Biol. 281, 285 (1998).

    Article  Google Scholar 

  9. 9

    V. I. Timofeev, Yu. A. Abramchik, I. V. Fateev, et al., Crystallogr. Rep. 58 (6), 842 (2013).

    ADS  Article  Google Scholar 

  10. 10

    M. J. Pugmire and S. E. Ealick, Structure 6, 1467 (1998).

    Article  Google Scholar 

  11. 11

    R. A. Norman, S. T. Barry, M. Bate, et al., Structure 12, 75 (2004).

    Article  Google Scholar 

  12. 12

    Omari. K. El, A. Bronckaers, S. Liekens, et al., Biochem. J. 399, 199 (2006).

  13. 13

    M. J. Pugmire and S. E. Ealick, Biochem. J. 361, 1 (2002).

    Article  Google Scholar 

  14. 14

    S. W. Rick, Y. G. Abashkin, R. L. Hilderbrandt, and S. K. Burt, PROTEINS: Struct., Funct., Genet. 37, 242 (1999).

    Article  Google Scholar 

  15. 15

    O. Trott and A. J. Olson, J. Comput. Chem. 31, 455 (2010).

    Google Scholar 

  16. 16

    V. Timofeev, Yu. Abramchik, N. Zhukhlistova, et al., Acta Crystallogr. D 70, 1155 (2014).

    Article  Google Scholar 

  17. 17

    I. Soteras Gutierrez, F.-Y. Lin, K. Vanommeslaeghe, et al., Bioorg. Med. Chem. (2016).

  18. 18

    W. L. Jorgensen, J. Chandrasekhar, J. D. Madura, et al., J. Chem. Phys. 79, 926 (1983).

    ADS  Article  Google Scholar 

  19. 19

    H. J. C. Berendsen, J. P. M. Postma, Gunsteren. W. F. van, et al., J. Chem. Phys. 81 (8), 3684 (1984). Bibcode:1984JChPh..81.3684B.

  20. 20

    M. Parrinello and A. Rahman, J. Chem. Phys. 76 (5), 2662 (1982).

    ADS  Article  Google Scholar 

  21. 21

    J. Mendieta, S. Martín-Santamaría, E.-M. Priego, et al., Biochemistry 43 (2), 409 (2004).

    Article  Google Scholar 

  22. 22

    N. G. Panova, K. S. Alekseev, A. S. Kuz’michev, et al., Biokhimiya 72 (1), 27 (2007).

    Google Scholar 

  23. 23

    N. Burton, M. Harrison, J. Hart, et al., Faraday Discuss. 110, 463 (1998).

    ADS  Article  Google Scholar 

Download references


This work was supported by the Ministry of Science and Higher Education within the State assignment FSRC “Crystallography and Photonics” RAS.

Author information



Corresponding author

Correspondence to I. P. Kuranova.

Additional information

Translated by T. Safonova

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Sidorov-Biryukov, D.D., Podshivalov, D.D., Timofeev, V.I. et al. Molecular Dynamics Study of Thymidine Phosphorylase from E. coli in the Apo Form and in Complexes with Substrates. Crystallogr. Rep. 64, 98–104 (2019).

Download citation