In silico identification, structure prediction and phylogenetic analysis of the 2'-O-ribose (cap 1) methyltransferase domain in the large structural protein of ssRNA negative-strand viruses.

The Escherichia coli RrmJ gene product has recently been shown to be the 23S rRNA:U2552 specific 2'-O-ribose methyltransferase (MTase) (RrmJ). Its structure has been solved and refined to 1.5 A resolution, demonstrating conservation of the three-dimensional fold and key catalytic side chains with the vaccinia virus VP39 protein, which functions as an mRNA 5'm(7)G-cap-N-specific 2'-O-ribose MTase. Using the amino acid sequence of RrmJ as an initial probe in an iterative search of sequence databases, we identified a homologous domain in the sequence of the L protein of non-segmented, negative-sense, single-stranded RNA viruses. The plausibility of the prediction was confirmed by homology modeling and checking whether important residues at substrate/ligand-binding sites were conserved. The predicted structural compatibility and the conservation of the active site between the novel putative MTase domain and genuine 2'-O-ribose MTases, together with the available results of biochemical studies, strongly suggest that this domain is a 5'm(7)G-cap-N-specific 2'-O-ribose MTase (i.e. the cap 1 MTase). Evolutionary relationships between these proteins are also discussed.

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