BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

Modeled structure of trypanothione reductase of Leishmania infantum

  • Singh, Bishal K. (Department of Biotechnology, Indian Institute of Technology Guwahati) ;
  • Sarkar, Nandini (Department of Biotechnology, Indian Institute of Technology Guwahati) ;
  • Jagannadham, M.V. (Molecular Biology Unit, Institute of Medical Sciences, Banaras Hindu University) ;
  • Dubey, Vikash K. (Department of Biotechnology, Indian Institute of Technology Guwahati)
  • Received : 2007.12.10
  • Accepted : 2008.01.11
  • Published : 2008.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Trypanothione reductase is an important target enzyme for structure-based drug design against Leishmania. We used homology modeling to construct a three-dimensional structure of the trypanothione reductase (TR) of Leishmania infantum. The structure shows acceptable Ramachandran statistics and a remarkably different active site from glutathione reductase(GR). Thus, a specific inhibitor against TR can be designed without interfering with host (human) GR activity.

Keywords

References

  1. Fairlamb, A. H. and Cerami, A. (1992) Metabolism and functions of trypanothione in the Kinetoplastida. Annu. Rev. Microbiol. 46, 695-729. https://doi.org/10.1146/annurev.mi.46.100192.003403
  2. Meister, A. (1989) Glutathione; Chemical, Biochemical and Medical Aspects, In: Dolphin, D., Poulson, R. and Avramovic, O., (eds). John Wiley, New York: 367-474.
  3. Ghisla, S. K. and Massey, V. (1989) Mechanism of flavoprotein- catalyzed reactions. Eur. J. Biochem. 181, 1-17. https://doi.org/10.1111/j.1432-1033.1989.tb14688.x
  4. Borges, A., Cunningham, M. L., Tovar, J. and Fairlamb, A. H. (1995) Site-directed mutagenesis of the redox-active cysteines of Trypanosoma cruzi trypanothione reductase. Eur. J. Biochem. 228, 745-752. https://doi.org/10.1111/j.1432-1033.1995.tb20319.x
  5. Muller, S., Liebau, E., Walter, R. D. and Krauth-Siegel, R. L. (2003) Thiol-based redox metabolism of protozoan parasites. Trends Parasitol. 19, 320-328. https://doi.org/10.1016/S1471-4922(03)00141-7
  6. Hunter, W. N., Bailey, S., Habash, J., Harrop, S. J., Helliwell, J. R., Aboagye-Kwarteng, T., Smith, K. and Fairlamb, A. H. (1992) Active site of trypanothione reductase: A target for rational drug design. J. Mol. Biol. 227, 322-333. https://doi.org/10.1016/0022-2836(92)90701-K
  7. Swindells, M. B. (1995) A procedure for the automatic determination of hydrophobic cores in protein structures. Protein Sci. 4, 93-102.
  8. Swindells, M. B. (1995) A procedure for detecting structural domains in proteins. Protein Sci. 4, 103-112. https://doi.org/10.1002/pro.5560040113
  9. Zhang, Y., Bond, C. S., Bailey, S., Cunningham, M. L., Fairlamb, A. H. and Hunter, W. N. (1996) The crystal structure of trypanothione reductase from the human pathogen Trypanosoma cruzi at 2.3 A resolution. Protein Sci. 5, 52-61. https://doi.org/10.1002/pro.5560050107
  10. Bailey, S., Fairlamb, A. H., Hunter, W. N. (1994) Structure of trypanothione reductase from Crithidia fasciculata at 2.6 A resolution; Enzyme-NADP interactions at 2.8 A resolution. Acta. Cryst. B50, 139-154
  11. Henderson, G. B., Murgolo, N. J., Kuriyan, J., Osapay, K., Kominos, D., Berry, A., Scrutton, N. S., Hinchliffe, N. W., Perham, R. N., Cerami, A. (1991) Engineering the substrate specificity of glutathione reductase toward that of trypanothione reduction. Proc. Natl. Acad. Sci. U.S.A. 88, 8769-8773. https://doi.org/10.1073/pnas.88.19.8769
  12. Bond, C. S., Zhang, Y., Berriman, M., Cunningham, M. L., Fairlamb, A. H., Hunter, W. N. (1999) Crystal structure of Trypanosoma cruzi trypanothione reductase in complex with trypanothione, and the structure-based discovery of new natural product inhibitors. Structure 7, 81-89. https://doi.org/10.1016/S0969-2126(99)80011-2
  13. Altschul, S. F., Madden, T. L., Schaffer, A. A., Zhang, Z., Miller, W., Lipman, D. J. (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 25, 3389-3402. https://doi.org/10.1093/nar/25.17.3389
  14. Sali, A. and Blundell, T. L. (1995) Comparative protein modelling by satisfaction of spatial restraints. J. Mol. Biol. 234, 779-815. https://doi.org/10.1006/jmbi.1993.1626
  15. Laskowski, R. A., MacArthur, M. W., Moss, D. S. and Thronton, J. M. (1993) PROCHECK: a program to check the stereochemical quality of protein structures. J. Appl. Cryst. 26, 283-291. https://doi.org/10.1107/S0021889892009944
  16. Ramachandran, G. N., Sasisekharan, V. (1968) Conformation of polypeptides and proteins. Adv. Protein Chem. 23, 283-438. https://doi.org/10.1016/S0065-3233(08)60402-7

Cited by

  1. Evaluation of plumbagin and its derivative as potential modulators of redox thiol metabolism of Leishmania parasite vol.110, pp.1, 2012, https://doi.org/10.1007/s00436-011-2498-x
  2. Molecular docking studies of selected tricyclic and quinone derivatives on trypanothione reductase ofLeishmania infantum 2010, https://doi.org/10.1002/jcc.21538
  3. Evaluation of selected antitumor agents as subversive substrate and potential inhibitor of trypanothione reductase: an alternative approach for chemotherapy of Leishmaniasis vol.352, pp.1-2, 2011, https://doi.org/10.1007/s11010-011-0762-0
  4. Structural modeling and docking studies of ribose 5-phosphate isomerase from Leishmania major and Homo sapiens: A comparative analysis for Leishmaniasis treatment vol.55, 2015, https://doi.org/10.1016/j.jmgm.2014.11.002
  5. Molecular docking and structure-based virtual screening studies of potential drug target, CAAX prenyl proteases, ofLeishmania donovani vol.34, pp.11, 2016, https://doi.org/10.1080/07391102.2015.1116411
  6. Studies on ornithine decarboxylase of Leishmania donovani: structure modeling and inhibitor docking vol.22, pp.1, 2013, https://doi.org/10.1007/s00044-012-0035-9
  7. Quantitative Proteome Analysis of Leishmania donovani under Spermidine Starvation vol.11, pp.4, 2016, https://doi.org/10.1371/journal.pone.0154262
  8. Footprinting of Inhibitor Interactions ofIn SilicoIdentified Inhibitors of Trypanothione Reductase ofLeishmaniaParasite vol.2012, 2012, https://doi.org/10.1100/2012/963658
  9. Purification, biochemical characterization and Insilico modeling of α-amylase from Vicia faba vol.234, 2017, https://doi.org/10.1016/j.molliq.2017.03.058
  10. Identification of active site residues of Fenugreek β-amylase: Chemical modification and in silico approach vol.83, 2014, https://doi.org/10.1016/j.plaphy.2014.08.005
  11. Leishmania–macrophage interactions: Insights into the redox biology vol.51, pp.2, 2011, https://doi.org/10.1016/j.freeradbiomed.2011.05.011
  12. In Silico Structural, Virtual Screening and Docking Studies of Human Cytochrome P450 2A7 Protein vol.7, pp.2, 2015, https://doi.org/10.1007/s12539-015-0007-0
  13. In silico prediction and characterization of 3D structure and binding properties of catalase from the commercially important crab, Scylla serrata vol.3, pp.2, 2011, https://doi.org/10.1007/s12539-011-0071-z
  14. Classification and structural analyses of mutational landscapes in hemochromatosis factor E protein: A protein defective in the hereditary hemochromatosis vol.6, 2017, https://doi.org/10.1016/j.genrep.2016.12.007
  15. Understanding the importance of conservative hypothetical protein LdBPK_070020 in Leishmania donovani and its role in subsistence of the parasite vol.596, 2016, https://doi.org/10.1016/j.abb.2016.02.025
  16. Rational Approaches for Drug Designing Against Leishmaniasis vol.160, pp.8, 2010, https://doi.org/10.1007/s12010-009-8764-z
  17. Mitogen-activated protein kinase 4 of Leishmania parasite as a therapeutic target vol.45, pp.12, 2010, https://doi.org/10.1016/j.ejmech.2010.09.020
  18. Epigallocatechin gallate, an active green tea compound inhibits the Zika virus entry into host cells via binding the envelope protein vol.104, 2017, https://doi.org/10.1016/j.ijbiomac.2017.06.105
  19. Fresh insights into the pyrimidine metabolism in the trypanosomatids vol.11, pp.1, 2018, https://doi.org/10.1186/s13071-018-2660-8