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A computer model-built structure of the T. congolense trypanothione reductase in complex with NADP

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Molecular Engineering

Abstract

A three-dimensional structure is engineered for the Trypanosoma congolense trypanothione reductase (TpR) using the sequence homology with glutathione reductase (GR) and lipoamide dehydrogenase, molecular graphics, energy optimization and molecular dynamics techniques. The model was extended to include the complex with the coenzyme nicotinamide adenine dinucleotide phosphate (NADP). The TpR-NADP structure is compared with X-ray data from the glutathione reductase complex with the reduced NADP (NADPH). A model of TpR-NADP including the trypanothione substrate is presented, and an electron-transfer mechanism is proposed.

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References

  1. R. L. Krauth-Siegel, B. Enders, G. B. Henderson, A. H. Fairlamb and R. H. Shirmer: Eur. J. Biochem. 164, 123 (1988).

    Google Scholar 

  2. C. Walsh, M. Bradley and K. Nadeau: TIBS 16, 305 (1991).

    Google Scholar 

  3. P. A. Karplus and G. E. Schulz: J. Mol. Biol. 195, 701 (1987).

    Google Scholar 

  4. S. Greer and R. N. Perthan: Biochemistry 25, 2736 (1986).

    Google Scholar 

  5. A. J. Schierbeek, M. B. A. Swarte, B. W. Dijkstra, G. Veiend, R. J. Read, W. G. J. Hol and J. Drenth: J. Mol. Biol. 206, 365 (1989).

    Google Scholar 

  6. A. Mattevi, A. J. Schierbeek and W. G. J. Hol: J. Mol. Biol. 220, 975 (1991).

    Google Scholar 

  7. J. Kuriyan, I. Wong, B. D. Guenther, N. J. Murgolo, A. Cerami and G. B. Henderson: J. Mol. Biol. 215, 335 (1990).

    Google Scholar 

  8. S. L. Shames, B. E. Kimmel, O. P. Peoples, N. Agabian and C. T. Walsh: Biochemistry 27, 50 (1988).

    Google Scholar 

  9. S. L. Shames, A. H. Fairlamb, A. Cerami and C. T. Walsh: Biochemistry 25, 3579 (1986).

    Google Scholar 

  10. E. Horjales and M. Paulino-Blumenfeld: International Symposium on Crystallography and Molecular Biology, Guaruja, SP, Brazil (1990).

  11. M. Paulino-Blumenfeld, N. Hikichi and M. Hansz: ‘Docking studies on inhibition of Glutathione Reductase by nitrofurans: Its relation with the active site of Trypanothione Reductase’ International Symposium on Crystallography and Molecular Biology’, Guaruja, SP, Brazil (1990).

  12. E. Horjales, F. M. L. G. Stamato and M. Paulino-Blumenfeld: ‘Comparacao de sitios ativos e relacão entre o mecanismo de acão das enzimas tripanotiona reductase, glutationa reductase e lipoamida desidrogenase’, Reunião Anual da SBQ, Caxambu, Brasil, (1991).

  13. S. L. Shames, B. C. Kimmel, O. P. Peoples, N. Agabian and C. T. Walsh: Biochemistry 27, 5014 (1988).

    Google Scholar 

  14. T. A. Jones: J. Appl. Cryst. 11, 268 (1978).

    Google Scholar 

  15. C. C. Cambillau and E. Horjales: J. Mol. Graph. 5, 174 (1987).

    Google Scholar 

  16. W. F.van Gunsteren and H. J. C. Berendsen: Groningen Molecular Simulation (GROMOS) Library Manual, BIOMOS B. V., Nijenborgh 16, Groningen The Netherlands, (1987).

    Google Scholar 

  17. O. Tapia and J. Åqvist: Prog. Clin. Biol. Res. 289, 55 (1989).

    Google Scholar 

  18. J. Åqvist, W. F.van Gunsteren, M. Leijonmarck and O. Tapia. J. Mol. Biol. 83, 461 (1985).

    Google Scholar 

  19. E. Horjales, J. Åqvist, M. Leijonmarck and O. Tapia: Biochem. Biophys. Res. Commun. 148, 954 (1987).

    Google Scholar 

  20. J. Åqvist, P. Sandbolm, T. A. Jones, M. E. Newcomer, W. F.van Gunsteren and O. Tapia: J. Mol. Biol. 192, 593 (1986).

    Google Scholar 

  21. J. Åqvist, M. Leijonmarck and O. Tapia: Eur. Biophys. J. 16, 327 (1989).

    Google Scholar 

  22. O. Nilsson, O. Tapia and W. F.van Gunsteren: Biochem. Biophys. Res. Comm. 171, 581 (1990).

    Google Scholar 

  23. D. W. Rice, G. E. Schulz and J. R. Guest: J. Mol. Biol. 174, 483 (1984).

    Google Scholar 

  24. M. Bradley, B. U.S. and C. T. Walsh: Biochemistry 30, 6124 (1991).

    Google Scholar 

  25. E. Pai, P. A. Karplus and G. E. Schulz: Biochemistry 27, 4465 (1988).

    Google Scholar 

  26. E. Pai and G. E. Schulz: J. Biol. Chem. 258, 1752 (1983).

    Google Scholar 

  27. G. E. Schulz, R. H. Schirmer and E. F. Pai: J. Mol. Biol. 160, 287 (1982).

    Google Scholar 

  28. M. Carson: J. Mol. Graph. 5, 103 (1987).

    Google Scholar 

  29. O. Tapia, R. Cardenas, J. Andres, J. Krechl, M. Campillo and F. Colonna-Cesari: Int. J. Quantum. Chem. 39, 767 (1991).

    Google Scholar 

  30. A. Heller: Acc. Chem. Res. 23, 128 (1990).

    Google Scholar 

  31. A. J. Prongay, D. R. Engelke, C. J. Williams: J. Biol. Chem. 264, 2656 (1989).

    Google Scholar 

  32. G. A. Petsko: Nature 352, 104 (1991).

    Google Scholar 

  33. J. Kuriyan, X.-P. Kong, T. S. R. Krisna, R. M. Sweet, N. J. Murgolo, H. Field, A. Cerami and G. B. Henderson: Proc. Natl. Acad. Sci. (USA) 88, 8764 (1991).

    Google Scholar 

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Author notes

  1. E. Horjales

    Present address: Departamento de Fisica, Facultad de Ciencias, Universidad de la Republica, Montevideo, Uruguay

Authors and Affiliations

  1. Departamento de Fisica e Ciencia dos Materials, Instituto de Fisica e Quimica de S. Carlos, 13560 S., Carlos, SP, Brasil

    E. Horjales

  2. Department of Physical Chemistry, Uppsala University, Box 532, S-751 21, Uppsala, Sweden

    B. Oliva, O. Nilsson & O. Tapia

  3. Departamento de Quimica, Universidade Federal de S. Carlos, C.P. 676, 13560 S., Carlos, SP, Brasil

    F. M. L. G. Stamato

  4. Facultad de Quimica, Universidad de la Republica, Montevideo, Uruguay

    M. Paulino-Blumenfeld

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  1. E. Horjales
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  4. M. Paulino-Blumenfeld
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  5. O. Nilsson
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  6. O. Tapia
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Horjales, E., Oliva, B., Stamato, F.M.L.G. et al. A computer model-built structure of the T. congolense trypanothione reductase in complex with NADP. Mol Eng 1, 357–375 (1992). https://doi.org/10.1007/BF00176807

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  • DOI: https://doi.org/10.1007/BF00176807

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