Abstract
X-ray crystallography is a technique which is finding increasing utility in the effort to find new antimalarial drugs. This is in spite of the serious difficulties often encountered in obtaining sufficient quantities of protein to crystallize. This review provides an overview of the Plasmodium falciparum proteins which have been crystallized with bound inhibitors and the methodology employed in the heterologous expression of these proteins. Lactate dehydrogenase, plasmepsin II, and triosphosphate isomerase are the most advanced targets of structure-based drug design, but nine other P. falciparum proteins have been crystallized with inhibitors as well, and this is clearly an area which is moving very quickly. Some consideration will also be given to the limitations of structure-based drug discovery with respect to known antimalarial drugs.
Keywords: adenylosuccinate synthetase, pfadss, crystallography, cyclophilin, pfcyp19, dihydrofolate reductase/thymidylate synthase, pfdhfr-ts, enoyl-acyl carrier reductase, pfenr, formylmethionine deformylase
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