Crystal structure of the dengue virus methyltransferase bound to a 5'-capped octameric RNA.

ABSTRACT: The N-terminal domain of the flavivirus NS5 protein functions as a methyltransferase (MTase). It sequentially methylates the N7 and 2'-O positions of the viral RNA cap structure (GpppA→(7me)GpppA→(7me)GpppA(2'-O-me)). The same NS5 domain could also have a guanylyltransferase activity (GTP+ppA-RNA→GpppA). The mechanism by which this protein domain catalyzes these three distinct functions is currently unknown. Here we report the crystallographic structure of DENV-3 MTase in complex with a 5'-capped RNA octamer (G(ppp)AGAACCUG) at a resolution of 2.9 A. Two RNA octamers arranged as kissing loops are encircled by four MTase monomers around a 2-fold non-crystallography symmetry axis. Only two of the four monomers make direct contact with the 5' end of RNA. The RNA structure is stabilised by the

SUBMITTER: Yap LJ 

PROVIDER: S-EPMC2941465 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature