The 2.2 A resolution crystal structure of influenza B neuraminidase and its complex with sialic acid.
Influenza virus neuraminidase catalyses the cleavage of terminal sialic acid, the viral receptor, from carbohydrate chains on glycoproteins and glycolipids. We present the crystal structure of the enzymatically active head of influenza B virus neuraminidase from the strain B/Beijing/1/87. The native structure has been refined to a crystallographic R-factor of 14.8% at 2.2 A resolution and its complex with sialic acid refined at 2.8 A resolution. The overall fold of the molecule is very similar to the already known structure of neuraminidase from influenza A virus, with which there is amino acid sequence homology of approximately 30%. Two calcium binding sites have been identified. One of them, previously undescribed, is located between the active site and a large surface antigenic loop. The calcium ion is octahedrally co-ordinated by five oxygen atoms from the protein and one water molecule. Sequence comparisons suggest that this calcium site should occur in all influenza A and B virus neuraminidases. Soaking of sialic acid into the crystals has enabled the mode of binding of the reaction product in the putative active site pocket to be revealed. All the large side groups of the sialic acid are equatorial and are specifically recognized by nine fully conserved active site residues. These in turn are stabilized by a second shell of 10 highly conserved residues principally by an extensive network of hydrogen bonds.
Burmeister
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EMBL Outstation, c/o ILL, Grenoble, France.
Ruigrok
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Cusack
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D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000276:immunology; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D003461:Crystallography; D006031:Glycosylation; D009981:Influenza B virus / Q000201:enzymology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid; D009439:Neuraminidase / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D011487:Protein Conformation; D012689:Sequence Homology, Nucleic Acid; D012794:Sialic Acids / Q000378:metabolism*
D000956:Antigens, Viral; D012794:Sialic Acids; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid; D002118:Calcium