title: Receptor recognition mechanism of human influenza A H1N1 (1918), avian influenza A H5N1 (2004), and pandemic H1N1 (2009) neuraminidase.
abstract: Influenza A neuraminidase (NA) is a target for anti-influenza drugs. The function of this enzyme is to cleave a glycosidic linkage of a host cell receptor that links sialic acid (Sia) to galactose (Gal), to allow the virus to leave an infected cell and propagate. The receptor is an oligosaccharide on the host cell surface. There are two types of oligosaccharide receptor; the first, which is found mainly on avian epithelial cell surfaces, links Sia with Gal by an α2,3 glycosidic linkage; in the second, found mainly on human epithelial cell surfaces, linkage is via an α2,6 linkage. Some researchers believe that NAs from different viruses show selectivity for each type of linkage, but there is limited information available to confirm this hypothesis. To see if the linkage type is more specific to any particular NA, a number of NA-receptor complexes of human influenza A H1N1 (1918), avian influenza A H5N1 (2004), and a pandemic strain of H1N1 (2009) were constructed using homology modeling and molecular dynamics simulation. The results show that the two types of receptor analogues bound to NAs use different mechanisms. Moreover, it was found that a residue unique to avian virus NA is responsible for the recognition of the Siaα2,3Gal receptor, and a residue unique to human virus NA is responsible for the recognition of Siaα2,6Gal. We believe that this finding could explain how NAs of different virus origins always possess some unique residues.
authors.affiliation: Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok, Thailand. g5084005@ku.ac.th
authors.forename: Nipa
authors.initials: N
authors.lastname: Jongkon
authors.forename: Chak
authors.initials: C
authors.lastname: Sangma
mesh_terms: D005690:Galactose / Q000378:metabolism; D053118:Influenza A Virus, H1N1 Subtype / Q000378:metabolism*; D053124:Influenza A Virus, H5N1 Subtype / Q000378:metabolism*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009439:Neuraminidase / Q000378:metabolism*; D009844:Oligosaccharides / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D009844:Oligosaccharides; D011991:Receptors, Virus; D014764:Viral Proteins; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid; D005690:Galactose