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A Role for the Protease Falcipain 1 in Host Cell Invasion by the Human Malaria Parasite

Science  06 Dec 2002:
Vol. 298, Issue 5600, pp. 2002-2006
DOI: 10.1126/science.1077426

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Abstract

Cysteine proteases of Plasmodium falciparum are required for survival of the malaria parasite, yet their specific cellular functions remain unclear. We used a chemical proteomic screen with a small-molecule probe to characterize the predominant cysteine proteases throughout the parasite life cycle. Only one protease, falcipain 1, was active during the invasive merozoite stage. Falcipain 1–specific inhibitors, identified by screening of chemical libraries, blocked parasite invasion of host erythrocytes, yet had no effect on normal parasite processes such as hemoglobin degradation. These results demonstrate a specific role for falcipain 1 in host cell invasion and establish a potential new target for antimalarial therapeutics.

  • * To whom correspondence should be addressed at M. Bogyo, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94043, USA. E-mail: dgreenb{at}itsa.ucsf.edu (D.C.G.) and mbogyo{at}biochem.ucsf.edu (M.B.)

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