Abstract of the PDB Structure's related Publication:
RNA triphosphatase is an essential mRNA processing enzyme that catalyzes the first step in cap formation. The 2.05 A crystal structure of yeast RNA triphosphatase Cet1p reveals a novel active site fold whereby an eight-stranded beta barrel forms a topologically closed triphosphate tunnel. Interactions of a sulfate in the center of the tunnel with a divalent cation and basic amino acids projecting into the tunnel suggest a catalytic mechanism that is supported by mutational data. Discrete surface domains mediate Cet1p homodimerization and Cet1p binding to the guanylyltransferase component of the capping apparatus. The structure and mechanism of fungal RNA triphosphatases are completely different from those of mammalian mRNA capping enzymes. Hence, RNA triphosphatase presents an ideal target for structure-based antifungal drug discovery.
S.cerevisiae Triphosphatase Cet1 and RNA guanylyltransferase (Ceg1) interact in vivo and in vitro to form a bifunctional mRNA capping enzyme complex (Haussmann et al. 2001 ) . Indeed, an Essential Function of Saccharomyces cerevisiae RNA Triphosphatase Cet1 Is to Stabilize RNA Guanylyltransferase Ceg1 against thermal inactivation. The guanylyltransferase activity of the mRNA capping -enzyme catalyzes the transfer of GMP from GTP to the 5' terminus of mRNA. In S.cerevisiae the activity is carried on the alpha subunit of the capping enzyme, the product of the CEG1 gene (Yamagishi et al. 1995) . 5' guanine - N7 cap is essential for all eukaryotic organisms examined thus far and is the first co-transcriptional modification of cellular pre-messenger RNA. It represses RNA polymerase II transcription in vivo, suggesting a bidirectional flow of information between capping and transcription. TPase. Hydrolyzes the 5'-triphosphate end of nascent pre-mRNA to a 5'-diphosphate. The role of Ceg1-Cet1 interaction is to allostericaly activate Cet1.