The catalytic sites of influenza virus neuraminidase are located on the upper corners of the box-shaped tetramer that forms the head of the molecule. Antigenic determinants form a nearly-continuous surface across the top of the monomer encircling the catalytic site. Approximately the same number of amino acid sequence changes occurred in these determinants between the years 1968 and 1975 as occurred in the antigenic sites of influenza virus haemagglutinin in the same period.

The three-dimensional X-ray structure of a complex of the potent neuraminidase inhibitor 4-guanidino-NeuSAc2en and influenza virus neuraminidase (Subtype N9) has been obtained utilizing diffraction data to 1.8 A resolution.The interactions of the inhibitor, solvent water molecules, and the active site residues have been accurately determined. Six water molecules bound in the native structure have been displaced by the inhibitor, and the active site residues show no significant conformational changes on binding. Sialic acid, the natural substrate, binds in a halfchair conformation that is isosteric to the inhibitor. The conformation of the inhibitor in the active site of the X-ray structure concurs with that obtained by theoretical calculations and validates the structure-based design of the inhibitor. Comparison of known high-resolution structures of neuraminidase subtypes N2, N9, and B shows good structural conservation of the active site protein atoms, but the location of the water molecules in the respective active sites is less conserved. In particular, the environment of the 4-guanidino group of the inhibitor is strongly conserved and is the basis for the antiviral action of the inhibitor across all presently known influenza strains. Differences in the solvent structure in the active site may be related to variation in the affinities of inhibitors to different subtypes of neuraminidase.

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The polypeptides of the trimeric seed storage protein phaseolin comprise two structurally similar units each made up of a beta‐barrel and an alpha‐helical domain. The beta‐barrel has the ‘jelly‐roll’ folding topology of the viral coat proteins and the alpha‐helical domain shows structural similarity to the helix‐turn‐helix motif found in certain DNA‐binding proteins.

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