Structure-Function of Falcipains: Malarial Cysteine Proteases

• Published in: Journal of Tropical Medicine
• Main Authors: Kailash C. Pandey, Rajnikant Dixit
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2012
• Subjects: Arctic medicine. Tropical medicine; RC955-962; Arctic
• Online Access: https://doi.org/10.1155/2012/345195; https://doaj.org/article/1e898ce8e69c452bbf88e3287dc8a9ee

Evidence indicates that cysteine proteases play essential role in malaria parasites; therefore an obvious area of investigation is the inhibition of these enzymes to treat malaria. Studies with cysteine protease inhibitors and manipulating cysteine proteases genes have suggested a role for cysteine proteases in hemoglobin hydrolysis. The best characterized Plasmodium cysteine proteases are falcipains, which are papain family enzymes. Falcipain-2 and falcipain-3 are major hemoglobinases of P. falciparum. Structural and functional analysis of falcipains showed that they have unique domains including a refolding domain and a hemoglobin binding domain. Overall, the complexes of falcipain-2 and falcipain-3 with small and macromolecular inhibitors provide structural insight to facilitate the design or modification of effective drug treatment against malaria. Drug development targeting falcipains should be aided by a strong foundation of biochemical and structural studies.