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Figure 2
Overall structure of the hRV-B14 3C protease bound to the AG7404 inhibitor. (A) Orthogonal views of the hRV-B14 3C protease–AG7404 complex structure with domain I in brown, domain II in green, and the linker region connecting the two domains in violet. The catalytic triad residues (Cys146, His40 and Glu71) are labeled and secondary structural elements (α-helices and β-strands) are annotated. AG7404 is depicted as a cyan stick model positioned within the active site. The blue box indicates a region showing minor conformational differences among protomers in the asymmetric unit. (B) Close-up view of the active site showing AG7404 covalently bonded to Cys146. A polder map was generated using phenix.polder after omitting Cys146 and AG7404, with the resulting electron density shown as a yellow mesh contoured at 3.0σ. The residues of the catalytic triad are in stick representation. (C) The superposition of the four protomers in the asymmetric unit, presenting structural conservation and minor conformational variability in the loop between αC and βaII (blue box). The AG7404 molecules are shown as stick models bound at identical positions across all protomers. (D) Sequence alignment of hRV-B14, hRV-A16 and hRV-A21 3C proteases with secondary structural annotations derived from the hRV-B14 structure. Conserved residues are shaded in gray and black. The flexible region in the superposition of the four protomers is indicated by a blue box. The variable regions (VR1: residues 91–97; VR2: residues 107–110) derived from sequence alignments between hRV serotypes are underlined in orange. Catalytic residues (red circles) and AG7404-interacting residues (green diamonds) are highlighted.

IUCrJ
Volume 13| Part 1| January 2026| Pages 19-30
ISSN: 2052-2525
https://doi.org/10.1107/S2052252525008929