FIG. 1.
Crystal structure of the WNV MTase and comparison with the DENV-2 MTase. (A) Ribbon representation of the crystal structure of the WNV MTase. The MTase structure is colored as follows: N-terminal domain, red; MTase core, green; C-terminal domain, cyan. The bound SAH is shown in ball-and-stick representation with atom colors as follows: carbon, yellow; oxygen, red; nitrogen, blue; sulfur, green. (B) A representative omit (Fo-Fc) electron density map (magenta) showing the bound SAH and its interactions with the MTase residues. Hydrogen bonds are shown as orange dashed lines. (C) Superposition of the crystal structures of the DENV-2 (2) (pink) and WNV (cyan and red) MTases. Ribavirin (occupying the putative GTP cap-binding site for the 2′-O methylation) (see Fig. 8) and SAH are shown in ball-and-stick representation. The loops of the WNV structure that show significant differences relative to the DENV-2 structure are colored in red. (D and E) Solvent-accessible molecular GRASP (27) surface representation of the electrostatic potential of the WNV (D) and DENV-2 (E) MTases, showing the putative RNA substrate binding site. The surface is colored blue for positive (15 kT), red for negative (−15 kT) and white for neutral, where k is the Boltzmann constant and T is the temperature (27). In panels D and E, ribavirin and SAH are in stick representation with atom colors as follows: oxygen, red; nitrogen, blue; carbon, white; sulfur, green.