Evaluation of cysteine proteases of Plasmodium vivax as antimalarial drug targets: sequence analysis and sensitivity to cysteine protease inhibitors

Parasitology Research
Byoung-Kuk NaYoon Kong

Abstract

Cysteine proteases perform critical roles in the life cycles of malaria parasites. In Plasmodium falciparum, treatment of cysteine protease inhibitors inhibits hemoglobin hydrolysis and blocks the parasite development in vitro and in vivo, suggesting that plasmodial cysteine proteases may be interesting targets for new chemotherapeutics. To determine whether sequence diversity may limit chemotherapy against Plasmodium vivax, we analyzed sequence variations in the genes encoding three cysteine proteases, vivapain-1, -2 and -3, in 22 wild isolates of P. vivax. The sequences were highly conserved among wild isolates. A small number of substitutions leading to amino acid changes were found, while they did not modify essential residues for the function or structure of the enzymes. The substrate specificities and sensitivities to synthetic cysteine protease inhibitors of vivapain-2 and -3 from wild isolates were also very similar. These results support the suggestion that cysteine proteases of P. vivax are promising antimalarial chemotherapeutic targets.

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Citations

Oct 23, 2010·PLoS Neglected Tropical Diseases·Byoung-Kuk NaYoon Kong
Mar 20, 2010·Journal of Fish Diseases·M Pimenta LeibowitzD Zilberg
Jun 2, 2005·Journal of Inorganic Biochemistry·Raman K AfsharPradip K Mascharak
Sep 9, 2005·Angewandte Chemie·Carmen DrahlErik J Sorensen

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