Fig 2.

Structural analysis of treatment-emergent substitutions. X-ray crystallographic structure of danoprevir (green) bound to genotype 1b NS3/4A (gray) at 2.6 Å resolution, with positions I71, R155, D168, and I170 indicated (yellow, orange, red, yellow). (A) Semitransparent surface representation showing relative positions of treatment-emergent substitutions. Note that R155 and D168 are solvent exposed whereas I71 and I170 are interior to the protein. (B) Interaction of R155, D168 with danoprevir, and I170. R155 and D168 engage in salt bridge interactions (dashed red lines) responsible for forming a plane on which the P2 group of danoprevir lies. I170 abuts R155 and forms hydrophobic interactions with its side chain on the face opposite that of danoprevir.