Abstract
Malaria is one of the major diseases of the world. Between 2 to 3 million deaths occur each year, mainly children under 5 years of age living in sub-Saharan Africa. Up to 300 million people are infected at any given time and up to 2 billion people (close to half the world population) live in malarious areas and are at risk of infection. The most virulent of the four malaria species which infect humans is Plasmodium falciparum and the spread of resistance by this species to the available drugs, such as chloroquine, has resulted in a critical world health situation with a desperate need to develop new drugs.
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References
Ball, E. G., McKee, R. W., Anfinsen, C. B., Cruz, W. O. and Geumen, Q. M. (1948) Studies on malarial parasites IX. Chemical and metabolic changes during growth and multiplication in vivo and in vitro. J. Biol. Chem. 175,547–571.
Dame, J. B., Reddy, G. R., Yowell, C. A., Dunn, B. M., Kay, J. and Berry, C. (1994) Sequence, expression and modeled structure of an aspartic proteinase from the human malaria parasite Plasmodium falciparum. Mol. Biochem. Parasitol. 64, 177–90.
Divo, A., Geary, T., Davis, N. and Jensen, J. (1985) Nutritional requirements of Plasmodium falciparum in culture. I. Exogenously supplied dialyzable components necessary for continuous growth. J. Protozool. 32, 59–64.
Francis, S. E., Gluzman, I. Y., Oksman, A., Knickerbocker, A., Mueller, R., Bryant, M. L., Sherman, D. R., Russell, D. G. and Goldberg, D. E. (1994) Molecular characterization and inhibition of a Plasmodium falciparum aspartic hemoglobinase. EMBO J. 13, 306–17.
Fusek, M. and Vetvicka, V. (1995) Aspartic Proteinases: Physiology and Pathology. CRC Press Inc., Boca Raton, Florida.
Gluzman, I. Y, Francis, S. E., Oksman, A., Smith, C. E., Duffin, K. L. and Goldberg, D. E. (1994) Order and specificity of the Plasmodium falciparum hemoglobin degradation pathway. J. Clin. Invest. 93, 1602–8.
Goldberg, D. E., Slater, A. F., Beavis, R., Chait, B., Cerami, A. and Henderson, G. B. (1991) Hemoglobin degradation in the human malaria pathogen Plasmodium falciparum: a catabolic pathway initiated by a specific aspartic protease. J. Exp. Med. 173, 961–9.
Goldberg, D. E., Slater, A. F., Cerami, A. and Henderson, G. B. (1990) Hemoglobin degradation in the malaria parasite Plasmodium falciparum: an ordered process in a unique organelle. Proc. Natl. Acad. Sci. USA 87, 2931–5.
Groman, N. B. (1951) Dynamic aspects of the nitrogen metabolism of Plasmodium gallinaceum in vivo and in vitro. J. Infect. Dis. 88, 126–150.
Hill, J., Tyas, L., Phylip, L. H., Kay, J., Dunn, B. M. and Berry, C. (1994) High level expression and characterisation of Plasmepsin II, an aspartic proteinase from Plasmodium falciparum. FEBS Lett. 352, 155–8.
Luker, K., Francis, S., Gluzman, I. and Goldberg, D. (1996) Kinetic analysis of plasmepsins I and II aspartic proteases of the Plasmodium falciparum digestive vacuole. Mol. Biochem. Parasitol. 79, 71–8.
Moon, R. P., Tyas, L., Certa, U., Rupp, K., Bur, D., Jaquet, C, Matile, H., Loetscher, H., Grueninger-Leitch, F., Kay, J., Dunn, B. M., Berry, C. and Ridley, R. G. (1997) Recombinant expression and kinetic characterisation of plasmepsin I from Plasmodium falciparum. Eur. J. Biochem. 244, 552–560.
Olliaro, P. L. and Goldberg, D. E. (1995) The plasmodium digestive vacuole: Metabolic headquarters and choice drug target. Parasitology Today 11, 294–297.
Rangachari, K., Dluzewski, A., Wilson, R. and Gratzer, W. (1987) Cytoplasmic factor required for entry of malaria parasites into RBCs. Blood 70, 77–82.
Roth Jr., E., Brotman, D., Vanderberg, J. and Schulman, S. (1986) Malarial pigment-dependent error in the estimation of hemoglobin content in Plasmodium falciparum-mfecled red cells: implications for metabolic and biochemical studies of the erythrocytic phases of malaria. Am. J. Trop. Med. Hyg. 35, 906–11.
Scarborough, P. and Dunn, B. (1994) Redesign of the substrate specificity of human cathepsin D: the dominant role of position 287 in the S2 subsite. Protein Eng. 7, 495–502.
Schechter, I. and Berger, A. (1967) On the size of the active site in proteases. I. Papain. Biochem. Biophys. Res. Commun. 27, 157–62.
Silva, A. M., Lee, A. Y, Gulnik, S. V., Maier, P., Collins, J., Bhat, T. N., Collins, P. J., Cacheu, R. E., Kuker, K. Y. G. I. Francis, S. E., Oksman, A., Goldberg, D. E. and Erikson, J. W. (1996) Structure and inhibition of plasmepsin II, a hemoglobin-degrading enzyme from Plasmodium falciparum. Proc. Natl. Acad. Sci. USA 93, 10034–10039.
Vander Jagt, D. L., Hunsaker, L. A., Campos, N. M. and Scaletti, J. V. (1992) Localization and characterization of hemoglobin-degrading aspartic proteinases from the malarial parasite Plasmodium falciparum. Biochim. Biophys. Acta 1122, 256–264.
Zarchin, S., Krugliak, M. and Ginsburg, H. (1986) Digestion of the host erythrocyte by malaria parasites is the primary target for quinoline-containing antimalarials. Biochem. Pharmacol. 35, 2435–42.
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Moon, R.P. et al. (1998). Studies on Plasmepsins I and II from the Malarial Parasite Plasmodium falciparum and their Exploitation as Drug Targets. In: James, M.N.G. (eds) Aspartic Proteinases. Advances in Experimental Medicine and Biology, vol 436. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5373-1_56
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DOI: https://doi.org/10.1007/978-1-4615-5373-1_56
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