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1.  Reassignment of specificities of two cap methyltransferase domains in the reovirus lambda2 protein 
Genome Biology  2001;2(9):research0038.1-research0038.6.
Background
The reovirus λ2 protein catalyzes mRNA capping, that is, addition of a guanosine to the 5' end of each transcript in a 5'-to-5' orientation, as well as transfer of a methyl group from S-adenosyl-L-methionine (AdoMet) to the N7 atom of the added guanosyl moiety and subsequently to the ribose 2'-O atom of the first template-encoded nucleotide. The structure of the human reovirus core has been solved at 3.6 Å resolution, revealing a series of domains that include a putative guanylyltransferase domain and two putative methyltransferase (MTase) domains. It has been suggested that the order of domains in the λ2 protein corresponds to the order of reactions in the pathway and that the m7G (cap 0) and the 2'-O-ribose (cap 1) MTase activities may be exerted by the MTase 1 and the MTase 2 domains, respectively.
Results
We show that the reovirus MTase 1 domain shares a putative active site with the structurally characterized 2'-O-ribose MTases, including vaccinia virus cap 1 MTase, whereas the MTase 2 domain is structurally similar to glycine N-MTase.
Conclusions
On the basis of our analysis of the structural details we propose that the previously suggested functional assignments of the MTase 1 and MTase 2 domains should be swapped.
PMCID: PMC56899  PMID: 11574057
2.  mRNA:guanine-N7 cap methyltransferases: identification of novel members of the family, evolutionary analysis, homology modeling, and analysis of sequence-structure-function relationships 
BMC Bioinformatics  2001;2:2.
Background
The 5'-terminal cap structure plays an important role in many aspects of mRNA metabolism. Capping enzymes encoded by viruses and pathogenic fungi are attractive targets for specific inhibitors. There is a large body of experimental data on viral and cellular methyltransferases (MTases) that carry out guanine-N7 (cap 0) methylation, including results of extensive mutagenesis. However, a crystal structure is not available and cap 0 MTases are too diverged from other MTases of known structure to allow straightforward homology-based interpretation of these data.
Results
We report a 3D model of cap 0 MTase, developed using sequence-to-structure threading and comparative modeling based on coordinates of the glycine N-methyltransferase. Analysis of the predicted structural features in the phylogenetic context of the cap 0 MTase family allows us to rationalize most of the experimental data available and to propose potential binding sites. We identified a case of correlated mutations in the cofactor-binding site of viral MTases that may be important for the rational drug design. Furthermore, database searches and phylogenetic analysis revealed a novel subfamily of hypothetical MTases from plants, distinct from "orthodox" cap 0 MTases.
Conclusions
Computational methods were used to infer the evolutionary relationships and predict the structure of Eukaryotic cap MTase. Identification of novel cap MTase homologs suggests candidates for cloning and biochemical characterization, while the structural model will be useful in designing new experiments to better understand the molecular function of cap MTases.
doi:10.1186/1471-2105-2-2
PMCID: PMC35267  PMID: 11472630

Results 1-2 (2)