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

Protein Eng. 2002 Feb;15(2):101-8. doi: 10.1093/protein/15.2.101.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Genes, Viral*
  • Methyltransferases / chemistry*
  • Molecular Sequence Data
  • Molecular Structure
  • Mononegavirales / chemistry*
  • Mononegavirales / genetics*
  • Protein Folding
  • Sequence Homology, Amino Acid
  • Viral Structural Proteins / genetics*


  • Viral Structural Proteins
  • Methyltransferases
  • cap I RNA (nucleoside-2'-)methyltransferase