Structure-function of falcipains: Malarial cysteine proteases

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. copyright 2011 kailash c. pandey and rajnikant dixit.