Figure 4

Crystal structure of the DENV NS2B_H-NS3 protease showing the location of tryptophan residues.

(a) DENV-3 protease in complex with Bz-Nle-KRR-H inhibitor (PDB 3U1I)¹⁷. NS2B_H is shown in yellow and NS3pro in purple. The Ser83Trp mutation is shown in orange. (b) Ligand-free DENV-2 (PDB 2FOM-1)⁵. NS2B_H is shown in dark blue and NS3pro in light blue. Ser83 of NS2B_H and Trp5 of NS3pro are unresolved in the crystal structure. c) Alignment of ligand-bound and ligand-free NS2B_H-NS3pro. In the ligand-bound structure, the C-terminal region of NS2B_H (yellow) forms a β-hairpin which wraps around NS3pro. In the ligand-free structure, the C-terminal domain of NS2B_H (dark blue) does not engage with NS3pro. (d) Alignment of wild-type tryptophan residues of NS2B_H in yellow and black, and NS3pro in purple and blue for ligand-bound and ligand-free complexes respectively. Trp5 was unresolved in the ligand free crystal structure.