Aspartic Proteinases from the Human Malaria Parasite Plasmodium Falciparum

Abstract

The widespread occurrence of drug resistant parasites and insecticide resistant mosquitoes has resulted in a growing public health emergency in malaria control. In species of Plasmodium, aspartic proteinases have been implicated in processes such as release of merozoites from the late schizont stage (1) in invasion of the erythrocyte (2) and digestion of haemoglobin therein (3–5). Following ingestion, haemoglobin is degraded in the food vacuole, a specialised proteolytic organelle (3,4,6). The aspartic proteinase activity demonstrated to be present within this organelle was resolved into three peaks during partial purification (5), although full characterisation of these has yet to be accomplished. The key role of an aspartic proteinase in initiating haemoglobin digestion in the vacuole has been defined (6) and one aspartic proteinase (PFAPG) has been purified to apparent homogeneity from the food vacuoles of P. falciparum. The sequence of 22 residues at the N-terminus of the mature enzyme was determined, and its ability to initiate the degradation of haemoglobin by selective cleavage of the -Phe33 -Leu34 peptide bond located in the hinge region of the alpha-chain was demonstrated (6). Inhibition of haemoglobin catabolism or other essential functions catalysed by aspartic proteinases in the parasite offer attractive targets for therapeutic intervention.