Proteases in Malaria Parasites - A Phylogenomic Perspective

Abstract

Malaria continues to be one of the most devastating global health problems due to the high morbidity and mortality it causes in endemic regions. The search for new antimalarial targets is of high priority because of the increasing prevalence of drug resistance in malaria parasites. Malarial proteases constitute a class of promising therapeutic targets as they play important roles in the parasite life cycle and it is possible to design and screen for specific protease inhibitors. In this mini-review, we provide a phylogenomic overview of malarial proteases. An evolutionary perspective on the origin and divergence of these proteases will provide insights into the adaptive mechanisms of parasite growth, development, infection, and pathogenesis.B

Replication and maintenance of the Plasmodium falciparum apicoplast genome

“…Bioinformatic analysis suggests there are 21 proteases predicted to be targeted to the apicoplast, but their protein substrates and recognition sequences are unknown [27]. Western blot analysis has identified numerous cleavage products of Prex, although it is not clear which represent functional proteins.…”

Egress and invasion machinery of malaria: an in-depth look into the structural and functional features of the flap dynamics of plasmepsin IX and X

“…12 There are several enzymes in P. falciparum, that have been implicated in hemoglobin proteolysis, parasite nutrition and development, these enzyme families include; cysteine proteases; aspartic proteases; metalloproteases and dipeptidyl aminopeptidases. 13,14 Aspartic proteases, or plasmepsins, have been identied as key mediators of cellular processes, including hemoglobin degradation for the export of Plasmodium proteins that essential for parasite growth/survival 15 and particularly malarial egress and invasion. 16 P. falciparum possess a repertoire of 10 aspartic proteases (Plm I to X).…”

Antioxidant and Anti-Protease Activities of Diazepinomicin from the Sponge-Associated Micromonospora Strain RV115

“…Human cysteine cathepsins were reported to be associated with different mammalian tumors, suggesting their involvement in metastasis, angiogenesis and tumor progression [ 17 ]. Several protease inhibitors are in clinical phases for treatment of many diseases such as hypertension, diabetes, infectious diseases and cancer [ 18 , 19 ].…”