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Science. 2002 Dec 6;298(5600):2002-6.

A role for the protease falcipain 1 in host cell invasion by the human malaria parasite.

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  • 1Department of Pharmaceutical Chemistry, Veterans Affairs Medical Center, University of California, San Francisco, CA 94143, USA. dgreenb@itsa.ucsf.edu

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.

PMID:
12471262
[PubMed - indexed for MEDLINE]
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