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http://purl.uniprot.org/citations/11472630http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/11472630http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/11472630http://www.w3.org/2000/01/rdf-schema#comment"

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."xsd:string
http://purl.uniprot.org/citations/11472630http://purl.org/dc/terms/identifier"doi:10.1186/1471-2105-2-2"xsd:string
http://purl.uniprot.org/citations/11472630http://purl.org/dc/terms/identifier"doi:10.1186/1471-2105-2-2"xsd:string
http://purl.uniprot.org/citations/11472630http://purl.uniprot.org/core/author"Feder M."xsd:string
http://purl.uniprot.org/citations/11472630http://purl.uniprot.org/core/author"Feder M."xsd:string
http://purl.uniprot.org/citations/11472630http://purl.uniprot.org/core/author"Rychlewski L."xsd:string
http://purl.uniprot.org/citations/11472630http://purl.uniprot.org/core/author"Rychlewski L."xsd:string
http://purl.uniprot.org/citations/11472630http://purl.uniprot.org/core/author"Bujnicki J.M."xsd:string
http://purl.uniprot.org/citations/11472630http://purl.uniprot.org/core/author"Bujnicki J.M."xsd:string
http://purl.uniprot.org/citations/11472630http://purl.uniprot.org/core/author"Radlinska M."xsd:string
http://purl.uniprot.org/citations/11472630http://purl.uniprot.org/core/author"Radlinska M."xsd:string
http://purl.uniprot.org/citations/11472630http://purl.uniprot.org/core/date"2001"xsd:gYear
http://purl.uniprot.org/citations/11472630http://purl.uniprot.org/core/date"2001"xsd:gYear
http://purl.uniprot.org/citations/11472630http://purl.uniprot.org/core/name"BMC Bioinformatics"xsd:string
http://purl.uniprot.org/citations/11472630http://purl.uniprot.org/core/name"BMC Bioinformatics"xsd:string
http://purl.uniprot.org/citations/11472630http://purl.uniprot.org/core/pages"2"xsd:string
http://purl.uniprot.org/citations/11472630http://purl.uniprot.org/core/pages"2"xsd:string
http://purl.uniprot.org/citations/11472630http://purl.uniprot.org/core/title"mRNA:guanine-N7 cap methyltransferases: identification of novel members of the family, evolutionary analysis, homology modeling, and analysis of sequence-structure-function relationships."xsd:string
http://purl.uniprot.org/citations/11472630http://purl.uniprot.org/core/title"mRNA:guanine-N7 cap methyltransferases: identification of novel members of the family, evolutionary analysis, homology modeling, and analysis of sequence-structure-function relationships."xsd:string
http://purl.uniprot.org/citations/11472630http://purl.uniprot.org/core/volume"2"xsd:string
http://purl.uniprot.org/citations/11472630http://purl.uniprot.org/core/volume"2"xsd:string
http://purl.uniprot.org/citations/11472630http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/11472630
http://purl.uniprot.org/citations/11472630http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/11472630
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