Falcilysin

This chapter describes the structural chemistry and the biological aspects of falcilysin. Falcilysin consists of 1193 amino acids with a predicted mass of 138.8 kDa. The purified enzyme migrates at 125 kDa by SDS-PAGE and elutes as a monomer of 125 kDa by gel filtration. Falcilysin has a pi of 6.54. The active site has an HxxEH motif, like that of other M16 family members. The native enzyme is purified from P. falciparum food vacuoles, which are obtained by saponin lysis of harvested parasites. Long-term storage and maintenance of activity is achieved by adding l mg ml⁻¹ bovine serum albumin, 0.01% Tween-20 or 50 mM sodium acetate to the final purified product. Recombinant E. coli expression systems are being developed. Falcilysin is believed to lie downstream of other vacuolar proteases in the P. falciparum hemoglobin degradation pathway, as it lacks the ability to cleave intact hemoglobin or denatured globin. There appears to be only one FLN gene. This is distinct from the other food vacuolar proteases for which several paralogs have been documented to aid in hemoglobin digestion. Protease inhibitors targeting these other enzymes kill the parasite in culture.