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

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.

• Authors: Doron C Greenbaum, Amos Baruch, Munira Grainger, Zbynek Bozdech, Katlin F Medzihradszky, Juan Engel, Joseph DeRisi, Anthony A Holder, Matthew Bogyo
• Journal: Science (New York, N.Y.) (Science) Vol. 298 Issue 5600 Pg. 2002-6 (Dec 06 2002) ISSN: 1095-9203 [Electronic] United States
• PMID: 12471262 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cysteine Proteinase Inhibitors
• Hemoglobins
• Cysteine Endopeptidases
• falcipain
• falcipain 2
• falcipain 3
• Leucine
• aloxistatin

Topics

• Animals
• Cysteine Endopeptidases (isolation & purification, metabolism)
• Cysteine Proteinase Inhibitors (chemistry, pharmacology)
• Dose-Response Relationship, Drug
• Erythrocytes (parasitology)
• Fluorescent Antibody Technique
• Hemoglobins (metabolism)
• Humans
• Leucine (analogs & derivatives, pharmacology)
• Life Cycle Stages
• Organelles (enzymology)
• Plasmodium falciparum (drug effects, enzymology, growth & development, pathogenicity)
• Proteomics