Plasmepsin I (PMI), Plasmepsin II (PMII), and Plasmepsin IV (PMIV) (PM I, PM II, PM IV)

Plasmepsin I, II, and IV are aspartic proteases expressed in the digestive vacuole of Plasmodium falciparum during the asexual blood stage of malaria infection[3][4][5][7]. These enzymes initiate and catalyze the sequential degradation of host hemoglobin into peptides and amino acids, which are essential for parasite nutrition and growth[5][7]. They belong to the A1 pepsin-like family of aspartic proteases, sharing 50–70% sequence identity and structural features such as the bilobal fold common to pepsin proteases[5][6]. Inhibiting these enzymes halts hemoglobin digestion, leading to parasite death, which makes them major validated drug targets in the search for new antimalarials[5][6]. However, designing selective inhibitors is challenging due to their structural similarity to human aspartic proteases[6]. Peptidomimetic inhibitors such as pepstatin and certain HIV protease inhibitors can inhibit plasmepsins, and structure-based drug design efforts are ongoing to develop compounds with clinical utility in malaria therapy[3][6].

Other names

Plasmodium falciparum aspartic protease I (PM I)Plasmodium falciparum aspartic protease II (PM II)Plasmodium falciparum aspartic protease IV (PM IV)Plasmodium digestive vacuolar aspartic proteasePlasmodium digestive plasmepsins

Competitive inhibition of aspartic protease active site Blockade of hemoglobin degradation pathway in the malaria parasite