Skip to main content

Biophysical and Folding Parameters of Trypanothione Reductase from Leishmania infantum

Applied Biochemistry and Biotechnology volume 165, Article number: 13 (2011) Cite this article

Abstract

Out of various tropical diseases caused by trypanosomatids, leishmaniasis is a life-threatening disease caused by the leishmania parasite. We are targeting the thiol metabolic pathway of the parasite for drug development, and trypanothione reductase (TryR) is a key enzyme of this pathway. It is important to gather significant knowledge about biophysical and intrinsic properties of this enzyme which will be helpful in better understanding of this drug-target enzyme. We report here the modulation of activity and stability of TryR from Leishmania infantum in the presence of various denaturants and pHs. The enzyme is quite stable under high concentration of denaturants and showed better stability compared to TryR of Leishmania donovani, whose sequence differs at only on position (Ala363→Gly). Structural basis of the destabilizing effects is discussed.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig 4
Fig. 5

References

  1. Fairlamb, A. H., & Cerami, A. (1992). Annual Review of Microbiology, 46, 695–729.

    Article  CAS  Google Scholar 

  2. Zhang, Y., Bond, C. S., Bailey, S., Cunningham, M. L., Fairlamb, A. H., & Hunter, W. N. (1996). Protein Science, 5, 52–61.

    Article  Google Scholar 

  3. Desjeux, P. (1992). World Health Statistics, 45, 267–275.

    CAS  Google Scholar 

  4. Tempone, A. G., Borboremab, S. E., deAndrade, H. F., Amorim Gualda, N. C., Yogi, A., Carvalho, C. S., et al. (2005). Phytomedicine, 12, 382–390.

    Article  CAS  Google Scholar 

  5. Delgado, J., Macias, J., Pineda, J. A., Corzo, J. E., Gonzalez-Moreno, M. P., de la Rosa, R., et al. (1999). American Journal of Medicine and Hygiene, 61, 766–769.

    CAS  Google Scholar 

  6. Henderson, G. B., Fairlamb, A. H., & Cerami, A. (1987). Molecular and Biochemical Parasitology, 24, 39–45.

    Article  CAS  Google Scholar 

  7. Shukla, A. K., Singh, B. K., Patra, S., & Dubey, V. K. (2010). Applied Biochemistry and Biotechnology, 160, 2208–2218.

    Article  CAS  Google Scholar 

  8. Ghisla, S., & Massey, V. (1989). European Journal of Biochemistry, 181, 1–17.

    Article  CAS  Google Scholar 

  9. Borges, A., Cunningham, M. L., Tovar, J., & Fairlamb, A. H. (1995). European Journal of Biochemistry, 228, 745–752.

    Article  CAS  Google Scholar 

  10. Fairlamb, A. H., Blackburn, P., Ulrich, P., Chait, B. T., & Cerami, A. (1985). Science, 227, 1485–1487.

    Article  CAS  Google Scholar 

  11. Krauth-Siegel, R. L., Enders, B., Henderson, G. B., Fairlamb, A. H., & Schirmer, R. H. (1987). European Journal of Biochemistry, 164, 123–128.

    Article  CAS  Google Scholar 

  12. Sarkar, N., Singh, A. N., & Dubey, V. K. (2009). Biological Chemistry, 390, 1057–1061.

    Article  CAS  Google Scholar 

  13. Pompea, D. V., Giuseppe, G., Vincenzo, G., Guido, B., Luigi, M., Mose, R., et al. (2002). The Biochemical Journal, 367, 857–863.

    Article  Google Scholar 

  14. Pace, C. N. (1975). CRC Crit. ReV. Biochem., 3, 1–43.

    Article  CAS  Google Scholar 

  15. Rai, S., Dwivedi, U. N., & Goyal, N. (2009). Biochimica et Biophysica Acta, 1794, 1474–1484.

    CAS  Google Scholar 

  16. Baiocco, P., Colotti, G., Franceschini, S., & Ilari, A. (2009). Journal of Medicinal Chemistry, 52, 2603–2612.

    Article  CAS  Google Scholar 

  17. Hamilton, C. J., Saravanamuthu, A., Eggleston, I. M., & Fairlamb, A. H. (2003). The Biochemical Journal, 369, 529–537.

    Article  CAS  Google Scholar 

  18. Schonbrunn, E., Eschenburg, S., Luger, K., Kabsch, W., & Amrhein, N. (2000). Proceedings of the National Academy of Sciences of the United States of America, 97, 6345–6349.

    Article  CAS  Google Scholar 

  19. Semisotnov, G. V., Rodionova, N. A., Razgulyaev, O. I., Uversky, V. N., Gripas, A. F., & Gilmanshin, R. I. (1991). Biopolymers, 31, 119–128.

    Article  CAS  Google Scholar 

  20. Mayo, S. L., & Baldwin, R. L. (1993). Science, 262, 873–876.

    Article  CAS  Google Scholar 

  21. Nandi, P. K., & Robinson, D. R. (1984). Biochemistry, 23, 6661–6668.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

Infrastructural facilities and research fellowship to AKS by the Indian Institute of Technology Guwahati is acknowledged. Financial support by the Department of Biotechnology, Government of India in the form of research grant to VKD (Project No.: BT/PR10966/MED/29/88/2008) is also acknowledged.

Author information

Affiliations

  1. Department of Biotechnology, Indian Institute of Technology Guwahati, Guwahati, 781039, Assam, India

    Anil Kumar Shukla, Sanjukta Patra & Vikash Kumar Dubey

Authors
  1. Anil Kumar Shukla
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sanjukta Patra
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vikash Kumar Dubey
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vikash Kumar Dubey.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Shukla, A.K., Patra, S. & Dubey, V.K. Biophysical and Folding Parameters of Trypanothione Reductase from Leishmania infantum . Appl Biochem Biotechnol 165, 13 (2011). https://doi.org/10.1007/s12010-011-9229-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12010-011-9229-8

Keywords

  • Protein stability
  • Protein
  • Folding
  • Leishmaniasis
  • Drug-target enzyme