Artemisinins are the last line of defense against drug-resistant malaria parasites. They selectively target an important protein in the parasite without affecting the protein's close relative in humans. A study in the July 2005 issue of Nature Structural & Molecular Biology now reveals the basis of this selectivity.
Artemisinins selectively block the activity of a calcium-pumping protein in malaria parasites. Sanjeev Krishna and colleagues show that a single amino acid residue in this protein can determine this selectivity. When this amino acid is mutated to the corresponding residue found in the related human protein, the activity of the mutant malarial calcium pump is no longer blocked by artemisinins.
This observation suggests that artemisinin resistance could readily develop because a single mutation in the calcium pump protein is all it would take to produce drug-resistant parasites, pointing to the urgent need to develop robust treatment against malaria.
Sanjeev Krishna (St. George's Hospital Medical School, London, UK)
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Also published online.
(C) Nature Structural & Molecular Biology press release.
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