A yeast-like mRNA capping apparatus in Plasmodium falciparum

Analysis of the mRNA capping apparatus of the malaria parasite Plasmodium f alciparum illuminates an evolutionary connection to fungi rather than metaz oans. We show that P. falciparum encodes separate RNA guanylyltransferase ( Pgt1) and RNA triphosphatase (Prt1) enzymes and that the triphosphatase com ponent is a member of the fungal/viral family of metal-dependent phosphohyd rolases, which are structurally and mechanistically unrelated to the cystei ne-phosphatase-type RNA triphosphatases found in metazoans and plants. Thes e results highlight the potential for discovery of mechanism-based antimala rial drugs designed to specifically block the capping of Plasmodium mRNAs. A simple heuristic scheme of eukaryotic phylogeny is suggested based on the structure and physical linkage of the triphosphatase and guanylyltransfera se enzymes that catalyze cap formation.