Fig. (3).

Inhibition of E1 ATPase activity. (A) Structures of the lead and optimized biphenylsulfonacetic acid inhibitors of the E1 ATPase activity with IC₅₀ values of 2.0µM and 4.0nM, respectively. (B) Crystal structure of the hexameric C-terminal helicase domain of bovine papillomavirus (BPV) E1 (PDB accession number 2GXA [173]). (C) Enlarged views of the ATP-binding pocket displaying the locations of the highly conserved catalytic Lys-439 (yellow), essential for ATP interaction and catalysis, and Met-441, (blue) important for the activity of biphenylsulfonacetic acid inhibitors. These residues are equivalent to Lys-484 and Tyr-486, respectively, in HPV6 E1. Bound ADP (red) is depicted in stick representation.