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Interdisciplinary Perspectives on Infectious Diseases
Volume 2014, Article ID 453186, 7 pages
http://dx.doi.org/10.1155/2014/453186
Review Article

Serine Proteases of Malaria Parasite Plasmodium falciparum: Potential as Antimalarial Drug Targets

Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400005, India

Received 25 October 2013; Revised 2 January 2014; Accepted 7 January 2014; Published 11 March 2014

Academic Editor: Mary E. Marquart

Copyright © 2014 Asrar Alam. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. G. Breman, “The ears of the hippopotamus: manifestations, determinants, and estimates of the malaria burden,” The American Journal of Tropical Medicine and Hygiene, vol. 64, no. 1-2, pp. 1–11, 2001. View at Google Scholar · View at Scopus
  2. WHO, “World malaria report,” 2013.
  3. J. F. Trape, F. Legros, P. Ndiaye et al., “Chloroquine-resistant Plasmodium falciparum malaria in Senegal,” Transactions of the Royal Society of Tropical Medicine and Hygiene, vol. 83, no. 6, p. 761, 1989. View at Publisher · View at Google Scholar · View at Scopus
  4. J. R. Zucker, T. K. Ruebush II, C. Obonyo, J. Otieno, and C. C. Campbell, “The mortality consequences of the continued use of chloroquine in Africa: experience in Siaya, Western Kenya,” The American Journal of Tropical Medicine and Hygiene, vol. 68, no. 4, pp. 386–390, 2003. View at Google Scholar · View at Scopus
  5. C. H. Sibley, J. E. Hyde, P. F. G. Sims et al., “Pyrimethamine-sulfadoxine resistance in Plasmodium falciparum: what next?” Trends in Parasitology, vol. 17, no. 12, pp. 582–588, 2001. View at Publisher · View at Google Scholar · View at Scopus
  6. C. Wongsrichanalai, A. L. Pickard, W. H. Wernsdorfer, and S. R. Meshnick, “Epidemiology of drug-resistant malaria,” Lancet Infectious Diseases, vol. 2, no. 4, pp. 209–218, 2002. View at Publisher · View at Google Scholar · View at Scopus
  7. F. Ter Kuile, N. J. White, P. Holloway, G. Pasvol, and S. Krishna, “Plasmodium falciparum: in vitro studies of the pharmacodynamic properties of drugs used for the treatment of severe malaria,” Experimental Parasitology, vol. 76, no. 1, pp. 85–95, 1993. View at Publisher · View at Google Scholar · View at Scopus
  8. N. J. White, “Qinghaosu (artemisinin): the price of success,” Science, vol. 320, no. 5874, pp. 330–334, 2008. View at Publisher · View at Google Scholar · View at Scopus
  9. W. Ittarat, A. L. Pickard, P. Rattanasinganchan et al., “Recrudescence in artesunate-treated patients with falciparum malaria is dependent on parasite burden not on parasite factors,” The American Journal of Tropical Medicine and Hygiene, vol. 68, no. 2, pp. 147–152, 2003. View at Google Scholar · View at Scopus
  10. M. A. Travassos and M. K. Laufer, “Resistance to antimalarial drugs: molecular, pharmacologic, and clinical considerations,” Pediatric Research, vol. 65, no. 5, pp. 64R–70R, 2009. View at Publisher · View at Google Scholar · View at Scopus
  11. A. M. Dondorp, F. Nosten, P. Yi et al., “Artemisinin resistance in Plasmodium falciparum malaria,” New England Journal of Medicine, vol. 361, no. 5, pp. 455–467, 2009. View at Publisher · View at Google Scholar · View at Scopus
  12. T. J. C. Anderson, S. Nair, S. Nkhorna et al., “High heritability of malaria parasite clearance rate indicates a genetic basis for artemisinin resistance in western Cambodia,” Journal of Infectious Diseases, vol. 201, no. 9, pp. 1326–1330, 2010. View at Publisher · View at Google Scholar · View at Scopus
  13. WHO, “Global report on antimalarial drug efficacy and drug resistance: 2000–2010,” 2010.
  14. WHO, Guidelines for the Treatment of Malaria, 2nd edition, 2010.
  15. B. Turk, “Targeting proteases: successes, failures and future prospects,” Nature Reviews Drug Discovery, vol. 5, no. 9, pp. 785–799, 2006. View at Publisher · View at Google Scholar · View at Scopus
  16. J. H. McKerrow, C. Caffrey, B. Kelly, P. Loke, and M. Sajid, “Proteases in parasitic diseases,” Annual Review of Pathology, vol. 1, pp. 497–536, 2006. View at Publisher · View at Google Scholar · View at Scopus
  17. M. Drag and G. S. Salvesen, “Emerging principles in protease-based drug discovery,” Nature Reviews Drug Discovery, vol. 9, no. 9, pp. 690–701, 2010. View at Publisher · View at Google Scholar · View at Scopus
  18. C. Flexner, G. Bate, and P. Kirkpatrick, “Tipranavir,” Nature Reviews Drug Discovery, vol. 4, no. 12, pp. 955–956, 2005. View at Publisher · View at Google Scholar · View at Scopus
  19. I. Melnikova, “Hepatitis C therapies,” Nature Reviews Drug Discovery, vol. 7, no. 10, pp. 799–800, 2008. View at Publisher · View at Google Scholar · View at Scopus
  20. C. G. Smith and J. R. Vane, “The discovery of captopril,” FASEB Journal, vol. 17, no. 8, pp. 788–789, 2003. View at Publisher · View at Google Scholar · View at Scopus
  21. I. Melnikova, “The anticoagulants market,” Nature Reviews Drug Discovery, vol. 8, no. 5, pp. 353–354, 2009. View at Publisher · View at Google Scholar · View at Scopus
  22. N. Alkhouri and N. N. Zein, “Protease inhibitors: silver bullets for chronic hepatitis C infection?” Cleveland Clinic Journal of Medicine, vol. 79, no. 3, pp. 213–222, 2012. View at Publisher · View at Google Scholar · View at Scopus
  23. A. J. P. Docherty, T. Crabbe, J. P. O'Connell, and C. R. Groom, “Proteases as drug targets,” Biochemical Society Symposium, no. 70, pp. 147–161, 2003. View at Google Scholar · View at Scopus
  24. P. J. Rosenthal, “Hydrolysis of erythrocyte proteins by proteases of malaria parasites,” Current Opinion in Hematology, vol. 9, no. 2, pp. 140–145, 2002. View at Publisher · View at Google Scholar · View at Scopus
  25. M. J. Blackman, “Proteases involved in erythrocyte invasion by the malaria parasite: function and potential as chemotherapeutic targets,” Current Drug Targets, vol. 1, no. 1, pp. 59–83, 2000. View at Google Scholar · View at Scopus
  26. S. Yeoh, R. A. O'Donnell, K. Koussis et al., “Subcellular discharge of a serine protease mediates release of invasive malaria parasites from host erythrocytes,” Cell, vol. 131, no. 6, pp. 1072–1083, 2007. View at Publisher · View at Google Scholar · View at Scopus
  27. S. Arastu-Kapur, E. L. Ponder, U. P. Fonović et al., “Identification of proteases that regulate erythrocyte rupture by the malaria parasite Plasmodium falciparum,” Nature Chemical Biology, vol. 4, no. 3, pp. 203–213, 2008. View at Publisher · View at Google Scholar · View at Scopus
  28. E. Di Cera, “Serine proteases,” IUBMB Life, vol. 61, no. 5, pp. 510–515, 2009. View at Publisher · View at Google Scholar · View at Scopus
  29. R. J. Siezen and J. A. M. Leunissen, “Subtilases: the superfamily of subtilisin-like serine proteases,” Protein Science, vol. 6, no. 3, pp. 501–523, 1997. View at Google Scholar · View at Scopus
  30. Z. Bozdech, M. Llinás, B. L. Pulliam, E. D. Wong, J. Zhu, and J. L. DeRisi, “The transcriptome of the intraerythrocytic developmental cycle of Plasmodium falciparum,” PLoS Biology, vol. 1, no. 1, article E5, 2003. View at Publisher · View at Google Scholar · View at Scopus
  31. K. G. le Roch, Y. Zhou, P. L. Blair et al., “Discovery of gene function by expression profiling of the malaria parasite life cycle,” Science, vol. 301, no. 5639, pp. 1503–1508, 2003. View at Publisher · View at Google Scholar · View at Scopus
  32. M. Llinás, Z. Bozdech, E. D. Wong, A. T. Adai, and J. L. DeRisi, “Comparative whole genome transcriptome analysis of three Plasmodium falciparum strains,” Nucleic Acids Research, vol. 34, no. 4, pp. 1166–1173, 2006. View at Publisher · View at Google Scholar · View at Scopus
  33. M. J. Pallen and B. W. Wren, “The HtrA family of serine proteases,” Molecular Microbiology, vol. 26, no. 2, pp. 209–221, 1997. View at Google Scholar · View at Scopus
  34. C. P. Ponting, “Evidence for PDZ domains in bacteria, yeast, and plants,” Protein Science, vol. 6, no. 2, pp. 464–468, 1997. View at Google Scholar · View at Scopus
  35. N. D. Rawlings, E. O'Brien, and A. J. Barrett, “MEROPS: the protease database,” Nucleic Acids Research, vol. 30, no. 1, pp. 343–346, 2002. View at Google Scholar · View at Scopus
  36. P. K. Harris, S. Yeoh, A. R. Dluzewski et al., “Molecular identification of a malaria merozoite surface sheddase,” PLoS Pathogens, vol. 1, no. 3, article e29, pp. 0241–0251, 2005. View at Publisher · View at Google Scholar · View at Scopus
  37. A. Alam, R. K. Bhatnagar, and V. S. Chauhan, “Expression and characterization of catalytic domain of Plasmodium falciparum subtilisin-like protease 3,” Molecular and Biochemical Parasitology, vol. 183, no. 1, pp. 84–89, 2012. View at Publisher · View at Google Scholar · View at Scopus
  38. A. Alam, R. K. Bhatnagar, U. Relan, P. Mukherjee, and V. S. Chauhan, “Proteolytic activity of Plasmodium falciparum subtilisin-like protease 3 on parasite profilin, a multifunctional protein,” Molecular and Biochemical Parasitology, vol. 191, no. 2, pp. 58–62, 2013. View at Publisher · View at Google Scholar
  39. M. Sajid, C. Withers-Martinez, and M. J. Blackman, “Maturation and specificity of Plasmodium falciparum subtilisin-like protease-1, a malaria merozoite subtilisin-like serine protease,” Journal of Biological Chemistry, vol. 275, no. 1, pp. 631–641, 2000. View at Publisher · View at Google Scholar · View at Scopus
  40. M. J. Blackman, H. Fujioka, W. H. L. Stafford et al., “A subtilisin-like protein in secretory organelles of Plasmodium falciparum merozoites,” Journal of Biological Chemistry, vol. 273, no. 36, pp. 23398–23409, 1998. View at Publisher · View at Google Scholar · View at Scopus
  41. C. Withers-Martinez, J. W. Saldanha, B. Ely, F. Hackett, T. O'Connor, and M. J. Blackman, “Expression of recombinant Plasmodium falciparum subtilisin-like protease-1 in insect cells. Characterization, comparison with the parasite protease, and homology modeling,” Journal of Biological Chemistry, vol. 277, no. 33, pp. 29698–29709, 2002. View at Google Scholar · View at Scopus
  42. L. Jean, F. Hackett, S. R. Martin, and M. J. Blackman, “Functional characterization of the propeptide of Plasmodium falciparum subtilisin-like protease-1,” Journal of Biological Chemistry, vol. 278, no. 31, pp. 28572–28579, 2003. View at Publisher · View at Google Scholar · View at Scopus
  43. Y. Li, Z. Hu, F. Jordan, and M. Inouye, “Functional analysis of the propeptide of subtilisin E as an intramolecular chaperone for protein folding. Refolding and inhibitory abilities of propeptide mutants,” Journal of Biological Chemistry, vol. 270, no. 42, pp. 25127–25132, 1995. View at Publisher · View at Google Scholar · View at Scopus
  44. H.-W. Huang, W.-C. Chen, C.-Y. Wu et al., “Kinetic studies of the inhibitory effects of propeptides subtilisin BPN' and carlsberg to bacterial serine proteases,” Protein Engineering, vol. 10, no. 10, pp. 1227–1233, 1997. View at Google Scholar · View at Scopus
  45. A. Boudreault, D. Gauthier, and C. Lazure, “Proprotein convertase PC1/3-related peptides are potent slow tight-binding inhibitors of murine PC1/3 and Hfurin,” Journal of Biological Chemistry, vol. 273, no. 47, pp. 31574–31580, 1998. View at Publisher · View at Google Scholar · View at Scopus
  46. Y. Yabuta, H. Takagi, M. Inouye, and U. Shinde, “Folding pathway mediated by an intramolecular chaperone: propeptide release modulates activation precision of pro-subtilisin,” Journal of Biological Chemistry, vol. 276, no. 48, pp. 44427–44434, 2001. View at Publisher · View at Google Scholar · View at Scopus
  47. M. Fugère, P. C. Limperis, V. Beaulieu-Audy et al., “Inhibitory potency and specificity of subtilase-like pro-protein convertase (SPC) prodomains,” Journal of Biological Chemistry, vol. 277, no. 10, pp. 7648–7656, 2002. View at Publisher · View at Google Scholar · View at Scopus
  48. M. J. Gardner, H. Tettelin, D. J. Carucci et al., “Chromosome 2 sequence of the human malaria parasite Plasmodium falciparum,” Science, vol. 282, no. 5391, pp. 1126–1132, 1998. View at Google Scholar
  49. E. Pizzi and C. Frontali, “Divergence of noncoding sequences and of insertions encoding nonglobular domains at a genomic region well conserved in plasmodia,” Journal of Molecular Evolution, vol. 50, no. 5, pp. 474–480, 2000. View at Google Scholar · View at Scopus
  50. L. Jean, C. Withers-Martinez, F. Hackett, and M. J. Blackman, “Unique insertions within Plasmodium falciparum subtilisin-like protease-1 are crucial for enzyme maturation and activity,” Molecular and Biochemical Parasitology, vol. 144, no. 2, pp. 187–197, 2005. View at Publisher · View at Google Scholar · View at Scopus
  51. S. Gemma, S. Giovani, M. Brindisi et al., “Quinolylhydrazones as novel inhibitors of Plasmodium falciparum serine protease PfSUB1,” Bioorganic & Medicinal Chemistry Letters, vol. 22, no. 16, pp. 5317–5321, 2012. View at Publisher · View at Google Scholar
  52. A. Ruecker, M. Shea, F. Hackett, C. Suarez, E. M. A. Hirst, and K. Milutinovic, “Proteolytic activation of the essential parasitophorous vacuole cysteine protease SERA6 accompanies malaria parasite egress from its host erythrocyte,” The Journal of Biological Chemistry, vol. 287, no. 45, pp. 37949–37963, 2012. View at Publisher · View at Google Scholar
  53. M. J. Blackman, H.-G. Heidrich, S. Donachie, J. S. McBride, and A. A. Holder, “A single fragment of a malaria merozoite surface protein remains on the parasite during red cell invasion and is the target of invasion-inhibiting antibodies,” Journal of Experimental Medicine, vol. 172, no. 1, pp. 379–382, 1990. View at Publisher · View at Google Scholar · View at Scopus
  54. V. K. Goel, X. Li, H. Chen, S.-C. Liu, A. H. Chishti, and S. S. Oh, “Band 3 is a host receptor binding merozoite surface protein 1 during the Plasmodium falciparum invasion of erythrocytes,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 9, pp. 5164–5169, 2003. View at Publisher · View at Google Scholar · View at Scopus
  55. X. Li, H. Chen, T. H. Oo et al., “A co-ligand complex anchors Plasmodium falciparum merozoites to the erythrocyte invasion receptor band 3,” Journal of Biological Chemistry, vol. 279, no. 7, pp. 5765–5771, 2004. View at Publisher · View at Google Scholar · View at Scopus
  56. M. A. Child, C. Epp, H. Bujard, and M. J. Blackman, “Regulated maturation of malaria merozoite surface protein-1 is essential for parasite growth,” Molecular Microbiology, vol. 78, no. 1, pp. 187–202, 2010. View at Publisher · View at Google Scholar · View at Scopus
  57. N. C. S. de Monerri, H. R. Flynn, M. G. Campos et al., “Global identification of multiple substrates for Plasmodium falciparum SUB1, an essential malarial processing protease,” Infection and Immunity, vol. 79, no. 3, pp. 1086–1097, 2011. View at Publisher · View at Google Scholar · View at Scopus
  58. C. Suarez, K. Volkmann, A. R. Gomes, O. Billker, and M. J. Blackman, “The malarial serine protease SUB1 plays an essential role in parasite liver stage development,” PLoS Pathogens, vol. 9, Article ID e1003811, 2013. View at Google Scholar
  59. L. Tawk, C. Lacroix, P. Gueirard et al., “A key role for Plasmodium subtilisin-like SUB1 in egress of malaria parasites from host hepatocytes,” The Journal of Biological Chemistry, vol. 288, no. 46, pp. 33336–33346, 2013. View at Publisher · View at Google Scholar
  60. C. Moneriz, J. Mestres, J. M. Bautista, A. Diez, and A. Puyet, “Multi-targeted activity of maslinic acid as an antimalarial natural compound,” FEBS Journal, vol. 278, no. 16, pp. 2951–2961, 2011. View at Publisher · View at Google Scholar · View at Scopus
  61. C. Withers-Martinez, C. Suarez, S. Fulle et al., “Plasmodium subtilisin-like protease 1 (SUB1): insights into the active-site structure, specificity and function of a pan-malaria drug target,” International Journal for Parasitology, vol. 42, no. 6, pp. 597–612, 2012. View at Publisher · View at Google Scholar
  62. S. Fulle, C. Withers-Martinez, M. J. Blackman, G. M. Morris, and P. W. Finn, “Molecular determinants of binding to the Plasmodium subtilisin-like protease 1,” Journal of Chemical Information and Modeling, vol. 53, no. 3, pp. 573–583, 2013. View at Publisher · View at Google Scholar
  63. P. Uzureau, J.-C. Barale, C. J. Janse, A. P. Waters, and C. B. Breton, “Gene targeting demonstrates that the Plasmodium berghei subtilisin PbSUB2 is essential for red cell invasion and reveals spontaneous genetic recombination events,” Cellular Microbiology, vol. 6, no. 1, pp. 65–78, 2004. View at Publisher · View at Google Scholar · View at Scopus
  64. J.-C. Barale, T. Blisnick, H. Fujioka et al., “Plasmodium falciparum subtilisin-like protease 2, a merozoite candidate for the merozoite surface protein 1-42 maturase,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 11, pp. 6445–6450, 1999. View at Publisher · View at Google Scholar · View at Scopus
  65. S. A. Howell, F. Hackett, A. M. Jongco et al., “Distinct mechanisms govern proteolytic shedding of a key invasion protein in apicomplexan pathogens,” Molecular Microbiology, vol. 57, no. 5, pp. 1342–1356, 2005. View at Publisher · View at Google Scholar · View at Scopus
  66. S. L. Fleck, B. Birdsall, J. Babon et al., “Suramin and suramin analogues inhibit merozoite surface protein-1 secondary processing and erythrocyte invasion by the malaria parasite Plasmodium falciparum,” Journal of Biological Chemistry, vol. 278, no. 48, pp. 47670–47677, 2003. View at Publisher · View at Google Scholar · View at Scopus
  67. S. Dutta, J. D. Haynes, A. Barbosa et al., “Mode of action of invasion-inhibitory antibodies directed against apical membrane antigen 1 of Plasmodium falciparum,” Infection and Immunity, vol. 73, no. 4, pp. 2116–2122, 2005. View at Publisher · View at Google Scholar · View at Scopus
  68. F. Hackett, M. Sajid, C. Withers-Martinez, M. Grainger, and M. J. Blackman, “PfSUB-2: a second subtilisin-like protein in Plasmodium falciparum merozoites,” Molecular and Biochemical Parasitology, vol. 103, no. 2, pp. 183–195, 1999. View at Publisher · View at Google Scholar · View at Scopus
  69. Y. He, Y. Chen, N. Oganesyan et al., “Solution NMR structure of a sheddase inhibitor prodomain from the malarial parasite Plasmodium falciparum,” Proteins, vol. 80, no. 12, pp. 2810–2817, 2012. View at Publisher · View at Google Scholar
  70. S. Urban, “Rhomboid proteins: conserved membrane proteases with divergent biological functions,” Genes and Development, vol. 20, no. 22, pp. 3054–3068, 2006. View at Publisher · View at Google Scholar · View at Scopus
  71. S. Singh, M. Plassmeyer, D. Gaur, and L. H. Miller, “Mononeme: a new secretory organelle in Plasmodium falciparum merozoites identified by localization of rhomboid-1 protease,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 50, pp. 20043–20048, 2007. View at Publisher · View at Google Scholar · View at Scopus
  72. P. Srinivasan, I. Coppens, and M. Jacobs-Lorena, “Distinct roles of Plasmodium rhomboid 1 in parasite development and malaria pathogenesis,” PLoS Pathogens, vol. 5, no. 1, Article ID e1000262, 2009. View at Publisher · View at Google Scholar · View at Scopus
  73. I. M. Vera, W. L. Beatty, P. Sinnis, and K. Kim, “Plasmodium protease rom1 is important for proper formation of the parasitophorous vacuole,” PLoS Pathogens, vol. 7, no. 9, Article ID e1002197, 2011. View at Publisher · View at Google Scholar · View at Scopus
  74. R. P. Baker, R. Wijetilaka, and S. Urban, “Two Plasmodium rhomboid proteases preferentially cleave different adhesins implicated in all invasive stages of malaria,” PLoS Pathogens, vol. 2, no. 10, p. e113, 2006. View at Publisher · View at Google Scholar · View at Scopus
  75. R. A. O'Donnell, F. Hackett, S. A. Howell et al., “Intramembrane proteolysis mediates shedding of a key adhesin during erythrocyte invasion by the malaria parasite,” Journal of Cell Biology, vol. 174, no. 7, pp. 1023–1033, 2006. View at Publisher · View at Google Scholar · View at Scopus