Plasmodium falciparum plasmepsin (Plm)

Plasmodium falciparum plasmepsins are a family of ten aspartic proteases that play indispensable roles throughout the life cycle of the malaria parasite. The most well-characterized members, including Plm I, II, IV, and the histo-aspartic protease (HAP), reside in the parasite's acidic food vacuole where they initiate the degradation of host hemoglobin to provide essential nutrients (UniProt: P22223). Beyond nutrition, Plm V is vital for the processing and export of parasite proteins into the host erythrocyte, a process necessary for host cell remodeling and virulence (PubMed: 25119035). Additionally, Plm IX and X have been identified as essential for the processes of parasite egress and invasion of red blood cells (PubMed: 29074583). Because these enzymes are critical for parasite survival and differ significantly from human aspartic proteases like cathepsin D, they are high-priority targets for antimalarial drug discovery. Inhibitors targeting these proteases aim to disrupt metabolic pathways and life cycle transitions, providing a strategy to overcome resistance to current antimalarial drugs (PubMed: 22403578).

Other names

Aspartic proteaseHemoglobinaseHisto-aspartic proteaseHAPPM

Inhibition of aspartic protease activity, which prevents the degradation of host hemoglobin or the export of essential parasite proteins, ultimately leading to parasite death.