Structure-based drug discovery for Plasmodium falciparum.
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.
Mehlin
Christopher
C
University of Washington, Structural Genomics of Pathogenic Protozoa, Box 357350 Department of Biochemistry, Seattle, WA 98195, USA. cmehlin@u.washington.edu
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry*; D018360:Crystallography, X-Ray; D010963:Plasmodium falciparum / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D015800:Protozoan Proteins / Q000737:chemistry
D000962:Antimalarials; D015800:Protozoan Proteins