Molecular Modeling of Sialyloligosaccharide Fragments into the Active site of Influenza Virus N9 Neuraminidase

Abstract

Molecular modeling studies have been carried out to investigate the interactions between substrate sialyloligosaccharide (SOS) fragments bearing different glycosidic linkages and influenza virus N9 neuraminidase, a surface glycoprotein of influenza virus subtype N9. The studies revealed that the allowed orientation for sialic acid (SA) is less than 1% in the Eulerian space at the active site. The active site of this enzyme has enough space to accommodate various SOS fragments, NeuNAcalpha(2-3)Gal, NeuNAcalpha(2-6)Gal, NeuNAcalpha(2-8)NeuNAc and NeuNAcalpha(2-9)NeuNAc, but on specific conformations. In the bound conformation, among these substrates there exists a conformational similarity leading to a structural similarity, which may be an essential requirement for the cleavage activity of the neuraminidases irrespective of the type of glycosidic linkage.

Influenza A Virus Neuraminidase Enhances Meningococcal Adhesion to Epithelial Cells through Interaction with Sialic Acid-Containing Meningococcal Capsules

“…To our knowledge, there are no available data on NA recognition of ␣2,9-linked sialic acids, which are typical of serogroup C capsules. However, molecular modeling studies showed that the active site of influenza virus N9 NA has enough space to accommodate substrates bearing the four types of glycosidic linkages (39). Whatever the serogroup, the exosialidase activity of the viral NA is unlikely to lead to a complete disruption of the capsule.…”