Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
4372260 | Experimental Parasitology | 2006 | 6 Pages |
Abstract
The Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3 are hemoglobinases and potential antimalarial drug targets. The falcipain-2â² gene was identified recently and is nearly identical in sequence to falcipain-2. The product of this gene has not been studied previously. The mature protease domain of falcipain-2â² was expressed in Escherichia coli, purified, and refolded to active enzyme. Functional analysis revealed similar biochemical properties to those of falcipain-2, including pH optima (pH 5.5-7.0), reducing requirements, and substrate preference. Studies with cysteine protease inhibitors showed similar inhibition of falcipain-2 and falcipain-2â², although specificities were not identical. Considering activity against the presumed biological substrate, both enzymes readily hydrolyzed hemoglobin. Our results confirm that falcipain-2â² is an active hemoglobinase and suggest that falcipain-2 and falcipain-2â² play similar roles in erythrocytic parasites but that, for promising cysteine protease inhibitors, it will be important to confirm activity against this additional target.
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Immunology and Microbiology
Parasitology
Authors
Naresh Singh, Puran S. Sijwali, Kailash C. Pandey, Philip J. Rosenthal,