RNA methyltransferases involved in 5' cap biosynthesis

Byszewska, Magdalena; Smietanski, Miroslaw; Purta, Elzbieta; Bujnicki, Janusz M

To date, numerous high-resolution structures of viral RNA capping enzymes have been determined, in particular for cap methyltransferases from various flaviviruses, which have been considered an attractive new antiviral target. 77 Based on knowledge of structures, efforts have been made toward the identification of specific inhibitors of these enzymes. For instance, a structure-based search for new inhibitors was performed for the dengue virus methyltransferase. [78] [79] [80] [81] The development of compounds that specifically inhibit viral methyltransferases will be aided by the recent structure determination of the catalytic domain of the human cap1 methyltransferase, which shares the global architecture, but exhibits a different cap-binding site compared to the viral enzymes. 39 The human cap1 methyltransferase appears to be essential and cannot be knocked out in human cells (our unpublished data), therefore the development of inhibitors specific against that human enzyme could be also useful as tools to study the cellular function of cap1 methylation.