Figure 8.

Comparison of Fingers-Thumb connection in different RdRP structures. (a) Two orthogonal views of the interactions at the top of the thumb in poliovirus (PV¹), rabbit hemorrhagic disease virus (RHDV⁵), and Norwalk virus (NWV⁶) polymerases. The index finger is colored green, the ring finger is colored yellow, and the thumb is shown as a grey surface with its tryptophan “hook” residue colored magenta. Note how a loop on the thumbs of the RHDV and NWV polymerases forms a flap over the top of the index finger that interacts with the hook residue, forming a small tunnel through which the index finger passes in a β-strand conformation. In Norwalk virus polymerase this loop also wraps around Trp29 from the index finger (cyan), further stabilizing the interaction. (b) Structures of the native fingers-thumb interaction in hepatitis C virus polymerase⁸ and a benzimidazole-based inhibitor complex³⁶ showing how this compound binds the top of the thumb where the index fingertip (λ1-loop) normally interacts.