Authors: | Ho, C. K.; Shuman, S. |
Article Title: | Trypanosoma brucei RNA triphosphatase: Antiprotozoal drug target and guide to eukaryotic phylogeny |
Abstract: | The mRNA capping apparatus of the protozoan parasite Trypanosoma brucei consists of separately encoded RNA triphosphatase and RNA guanylyltransferase enzymes. The triphosphatase TbCet1 is a member of a new family of metal-dependent phosphohydrolases that includes the RNA triphosphatases of fungi and the malaria parasite Plasmodium falciparum. The protozoal/fungal enzymes are 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 block the capping of pathogen-encoded mRNAs. We propose a scheme of eukaryotic phylogeny based on the structure of RNA triphosphatase and its physical linkage to the guanylyltransferase component of the capping apparatus. |
Keywords: | unclassified drug; nonhuman; drug targeting; molecular genetics; animal; metabolism; classification; antifungal agent; drug effect; enzymology; antiprotozoal agent; rna triphosphatase; trypanosoma brucei; trypanosoma; acid anhydride hydrolases; antiprotozoal agents; rna; chemistry; amino acid sequence; molecular sequence data; sequence homology, amino acid; messenger rna; eukaryota; nucleotide sequence; rna structure; sequence homology; plasmodium falciparum; enzyme structure; protozoa; fungi; enzymes; eukaryote; metazoa; phylogeny; plant; rna capping; drug products; guanylyltransferase; fungal enzyme; hydrolase; metazoon; rna guanylyltransferase; priority journal; article; trypanosoma brucei brucei; eukaryotic phylogeny; malaria control; metal dependent phosphohydrolase; protozoal protein; tbcet1 protein |
Journal Title: | Journal of Biological Chemistry |
Volume: | 276 |
Issue: | 49 |
ISSN: | 0021-9258 |
Publisher: | American Society for Biochemistry and Molecular Biology |
Date Published: | 2001-12-07 |
Start Page: | 46182 |
End Page: | 46186 |
Language: | English |
DOI: | 10.1074/jbc.M108706200 |
PUBMED: | 11553645 |
PROVIDER: | scopus |
DOI/URL: | |
Notes: | Export Date: 21 May 2015 -- Source: Scopus |