Structure-function analysis of vaccinia virus mRNA cap (guanine-N7) methyltransferase Journal Article
| Authors: | Zheng, S.; Shuman, S. |
| Article Title: | Structure-function analysis of vaccinia virus mRNA cap (guanine-N7) methyltransferase |
| Abstract: | The guanine-N7 methyltransferase domain of vaccinia virus mRNA capping enzyme is a heterodimer composed of a catalytic subunit and a stimulatory subunit. Structure-function analysis of the catalytic subunit by alanine scanning and conservative substitutions (49 mutations at 25 amino acids) identified 12 functional groups essential for methyltransferase activity in vivo, most of which were essential for cap methylation in vitro. Defects in cap binding were demonstrated for a subset of lethal mutants that displayed residual activity in vitro. We discuss our findings in light of a model of the Michaelis complex derived from crystal structures of AdoHcy-bound vaccinia cap methyltransferase and GTP-bound cellular cap methyltransferase. The structure-function data yield a coherent picture of the vaccinia cap methyltransferase active site and the determinants of substrate specificity and affinity. Published by Cold Spring Harbor Laboratory Press. Copyright © 2008 RNA Society. |
| Keywords: | controlled study; unclassified drug; gene mutation; methylation; mutation, missense; nonhuman; protein conformation; amino acid substitution; gene function; methyltransferase; methyltransferases; kinetics; messenger rna; adomet; virus rna; rna caps; rna, messenger; gene identification; recombinant proteins; vaccinia virus; crystal structure; models, molecular; dimerization; alanine; catalysis; rna structure; enzyme specificity; guanosine triphosphate; protein structure, quaternary; mutagenesis; rna, viral; gene activity; poxvirus; poxviridae; rna analysis; 7-methylguanosine; mrna processing; guanine n7 methyltransferase; genes, viral |
| Journal Title: | RNA |
| Volume: | 14 |
| Issue: | 4 |
| ISSN: | 1355-8382 |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Date Published: | 2008-04-01 |
| Start Page: | 696 |
| End Page: | 705 |
| Language: | English |
| DOI: | 10.1261/rna.928208 |
| PUBMED: | 18256245 |
| PROVIDER: | scopus |
| PMCID: | PMC2271365 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 4" - "Export Date: 17 November 2011" - "CODEN: RNARF" - "Source: Scopus" |
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