Figure 1

Observed conformational changes in the inhibitor-binding site of the non-mutated (left) and mutated (right) complexes of NA/inhibitors. Neuraminidase inhibitors are presented in colored sticks (oseltamivir: orange, peramivir: blue, zanamivir: yellow), other involved NA residues are presented in green line, except for residues Arg and Lys (mutation R289K) in magenta color. The grey cartoon-presented background is the H7N9 NA structure. All the interactions are shown in black dotted line. Oxygen atoms are in red, nitrogens are in blue, and hydrogens are in white. For simplicity, only hydrogens involved in the interactions are shown. (A) Occupation of the bulky residue Trp²⁹² in the empty space created by a substituted smaller residue Lys²⁸⁹ (R289K) and the change of N-terminal (yellow) conformation influenced contacts between oseltamivir and the H7N9 NA binding site. (B) Conformation of peramivir twists (small arrow) towards the empty space, causing it to interact with Glu⁴²² instead of Glu²⁷⁴. (C) Conformational change of Tyr⁴⁰¹ induces interaction between zanamivir and the substituted residue Lys²⁸⁹. However, this interaction also causes one hydrogen bond loss in total between zanamivir and the H7N9 NA.