title: 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.
abstract: 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.
authors.affiliation: Bioinformatics Laboratory, International Institute of Cell and Molecular Biology, ul. ks. Trojdena 4, 02-109 Warsaw, Poland. iamb@bioinfo.pl
authors.forename: Janusz M
authors.initials: JM
authors.lastname: Bujnicki
authors.forename: Leszek
authors.initials: L
authors.lastname: Rychlewski
mesh_terms: D000595:Amino Acid Sequence; D005814:Genes, Viral; D008780:Methyltransferases / Q000737:chemistry*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D018096:Mononegavirales / Q000737:chemistry* / Q000235:genetics*; D017510:Protein Folding; D017386:Sequence Homology, Amino Acid; D015678:Viral Structural Proteins / Q000235:genetics*
chemical_list: D015678:Viral Structural Proteins; D008780:Methyltransferases; C032117:cap I RNA (nucleoside-2'-)methyltransferase