The malaria parasite exports hundreds of proteins to the red blood cell in order to commandeer the host cell for its own nefarious purposes. This proposal aims to study a protease called plasmepsin V. It has recently been discovered that plasmepsin V recognizes and cleaves a sequence on the proteins that the parasite has designated for export. This is crucial for proteins to get out into the host cell. The proposal addresses the questions: What is special about plasmepsin V compared with mammalian counterparts? What is the specificity of this enzyme for its substrate? How does plasmepsin V interact with other cellular components to ensure that proteins to be exported get to their destination? The proposed experiments will involve enzymology, site-directed mutagenesis and protein-protein interaction studies. The goal is to understand plasmepsin V function to inform antimalarial drug development efforts.

Public Health Relevance

Malaria afflicts hundreds of millions of people worldwide and over a thousand a year in this country, mostly those that have recently been abroad. Because of drug resistance there is a desperate need for new antimalarial treatments. The proposed research will study an important new target for drug development.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Study Section
Special Emphasis Panel (ZRG1-PTHE-N (09))
Program Officer
Mcgugan, Glen C
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Washington University
Schools of Medicine
Saint Louis
United States
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