Trypanosoma brucei RNA triphosphatase - Antiprotozoal drug target and guide to eukaryotic phylogeny

The mRNA capping apparatus of the protozoan parasite Trypanosoma brucei con sists of separately encoded RNA triphosphatase and RNA guanylyltransferase enzymes. The triphosphatase ThCet1 is a member of a new family of metal-dep endent phosphohydrolases that includes the RNA triphosphatases of fungi and the malaria parasite Plasmodium falciparum. The protozoal/fungal enzymes a re structurally and mechanistically unrelated to the RNA triphosphatases of metazoans and plants. These results highlight the potential for discovery of broad spectrum antiprotozoal and antifungal. drugs that selectively bloc k the capping of pathogen-encoded mRNAs. We propose a scheme of eukaryotic phylogeny based on the structure of RNA triphosphatase and its physical lin kage to the guanylyltransferase component of the capping apparatus.