Structure and mechanism of mRNA cap (Guanine-N7) methyltransferase Journal Article
| Authors: | Fabrega, C.; Hausmann, S.; Shen, V.; Shuman, S.; Lima, C. D. |
| Article Title: | Structure and mechanism of mRNA cap (Guanine-N7) methyltransferase |
| Abstract: | A suite of crystal structures is reported for a cellular mRNA cap (guanine-N7) methyltransferase in complex with AdoMet, AdoHcy, and the cap guanylate. Superposition of ligand complexes suggests an in-line mechanism of methyl transfer, albeit without direct contacts between the enzyme and either the N7 atom of guanine (the attacking nucleophile), the methyl carbon of AdoMet, or the sulfur of AdoMet/AdoHcy (the leaving group). The structures indicate that catalysis of cap N7 methylation is accomplished by optimizing proximity and orientation of the substrates, assisted by a favorable electrostatic environment. The enzyme-ligand structures, together with new mutational data, fully account for the biochemical specificity of the cap guanine-N7 methylation reaction, an essential and defining step of eukaryotic mRNA synthesis. |
| Keywords: | unclassified drug; gene mutation; methylation; animals; complex formation; structure-activity relationship; methyltransferases; amino acid sequence; molecular sequence data; sequence homology, amino acid; messenger rna; rna caps; s-adenosylhomocysteine; eukaryota; substrate specificity; ligand; ligands; crystal structure; models, molecular; crystallography, x-ray; binding sites; alanine; catalysis; point mutation; enzyme structure; biochemistry; protein structure, secondary; eukaryote; electricity; guanine derivative; s-adenosylmethionine; rna cap analogs; s adenosylmethionine; s adenosylhomocysteine; protozoan proteins; messenger rna synthesis; atom; electrostatics; guanosine phosphate; encephalitozoon cuniculi; article; guanine 7 methyltransferase |
| Journal Title: | Molecular Cell |
| Volume: | 13 |
| Issue: | 1 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2004-01-16 |
| Start Page: | 77 |
| End Page: | 89 |
| Language: | English |
| DOI: | 10.1016/s1097-2765(03)00522-7 |
| PROVIDER: | scopus |
| PUBMED: | 14731396 |
| DOI/URL: | |
| Notes: | Mol. Cell -- Cited By (since 1996):65 -- Export Date: 16 June 2014 -- CODEN: MOCEF -- Source: Scopus |
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