Structure-Function of Falcipains : Malarial Cysteine Proteases

Abstract EN

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.