Plasmepsin II

This chapter presents an overview of the structural chemistry and the biological aspects of plasmepsin II. A major physiological role for the plasmepsin II enzyme is thought to be the degradation of hemoglobin in infected human red blood cells. Plasmepsin II is capable of cleaving native human hemoglobin and acid-denatured globin, with a pH optimum around 5. Incubation with hemoglobin results in proteolysis at 3–4 sites, showing a preference for hydrophobic P2, P1 and P1′ residues. Native plasmepsin II can be prepared in nanogram to low microgram amounts from cultured intra-erythrocytic organisms. A high-level expression of a recombinant zymogen form has been achieved in E. coli. Proenzyme should be stored at –20°C in 50% glycerol; freezing without glycerol destroys the activity. Mature proteinase can be produced by autoactivation at pH 4.7 and is 12 residues longer at its N-terminus than naturally occurring plasmepsin II. Plasmepsin II has been shown to degrade spectrin in vitro at pH 6.8, a pH value likely to be similar to that of the red cell cytoplasm.