FIG 1.

(A) Overall structure of HCV NS5B highlighting some of the stabilizing interactions of the C-terminal domains. The β-loop and C-terminal arm regions are highlighted in black, residue Y448 is represented in blue, W550 is indicated in green, and D559 is shown as blue sticks and spheres. “DD” indicates the NS5B active site aspartate residues. (B) Closeup view of Y448 and the surrounding NS5B residues. The backbone oxygen of Y195 (atom colors) in the palm domain forms a hydrogen bond with Y448 OH1 (shown in blue). (C) Conserved residues on the C-terminal arm (L547 and F551 [shown in dark gray]) and on the thumb domain (I413, M414, I462, and L466 [shown in light gray]) form a deep hydrophobic pocket around W550. (D) Closeup view of interactions around D559. Residues S96, R168, and K172 in the finger domain, which form hydrogen bonds with D559, are shown in black. All figures were rendered with PyMol.