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Higher catalytic efficiency of N-7-methylation is responsible for processive N-7 and 2′-O methyltransferase activity in dengue virus
- Source :
-
Virology . Jun2010, Vol. 402 Issue 1, p52-60. 9p. - Publication Year :
- 2010
-
Abstract
- Abstract: Methyltransferases (MTases) from the genus Flavivirus encode both N-7 and 2′-O activities needed for type 1 (m7GpppNm) cap structure formation. We performed kinetic studies to understand the mechanisms of its progressive N-7 and 2′-O methylations. Sequential N-7 to 2′-O methylation occurred via a random bi bi and processive mechanism that does not involve enzyme–RNA dissociation. Analyses of steady state kinetic parameters showed that N-7 precedes 2′-O methylation as it turnovers RNA faster (k cat) resulting in 2.4-fold higher catalytic efficiency. Michaelis constants for S-adenosyl-methionine (AdoMet) in both reactions were about 10-fold lower than for their respective RNA substrates, suggesting that the rate-limiting steps in methylase reactions were associated with RNA templates. In the context of long viral RNA sequences, and compared to S-adenosyl-homocysteine, sinefungin was about 60- and 12-folds more potent against dengue N-7 and 2′-O MTase activity, exhibiting IC50 values of 30 and 41nM, respectively. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 00426822
- Volume :
- 402
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Virology
- Publication Type :
- Academic Journal
- Accession number :
- 50734119
- Full Text :
- https://doi.org/10.1016/j.virol.2010.03.011