| 1NCB |
Hydrolase(O-Glycosyl) |
date |
Jan 21, 1992 
 |
|---|
| title | Crystal Structures Of Two Mutant Neuraminidase-Antibody Complexes With Amino Acid Substitutions In The Interface |
| authors | W.R.Tulip, J.N.Varghese, P.M.Colman |
| compound |
source |
Molecule: Influenza A Subtype N9 Neuraminidase
Chain: N
Ec: 3.2.1.18
|
Organism_scientific: Influenza A Virus (Aternaustraliag70c1975(H11n9));
Organism_taxid: 384509
Strain: (Aternaustraliag70c1975(H11n9))
|
Molecule: Igg2a-Kappa Nc41 Fab (Light Chain)
Chain: L
|
Organism_scientific: Mus Musculus
Organism_common: House Mouse
Organism_taxid: 10090
|
Molecule: Igg2a-Kappa Nc41 Fab (Heavy Chain)
Chain: H
|
Organism_scientific: Mus Musculus
Organism_common: House Mouse
Organism_taxid: 10090
|
| symmetry | Space Group: P 4 21 2
|
| R_factor | 0.165 |
R_Free | NULL |
|
crystal
cell |
| length a |
length b |
length c |
angle alpha |
angle beta |
angle gamma |
| 167.000 |
167.000 |
124.000 |
90.00 |
90.00 |
90.00 |
|
| method | X-Ray Diffraction | resolution | 2 Å |
| ligand | BMA, CA, MAN, NAG
| enzyme | Exo-alpha-sialidase;. Neuraminidase;. Sialidase;. Alpha-neuraminidase;. Acetylneuraminidase. Hydrolase
E.C.3.2.1.18
BRENDA
|
| related structures | by homologous chain: 1IGJ, 1IKF, 1INY, 1IQW, 1NCA |
| domain | The transmembrane domain also plays a role in lipid raft association (by similarity). Intact n-terminus is essential for virion morphogenesis. Possess two apical sorting signals, one in the ectodomain, which is likely to be a glycan, and the other in the transmembrane domain. |
| similarity | Belongs to the glycosyl hydrolase 34 family.[Neur] |
| subunit | Homotetramer (by similarity). |
| catalytic activ. | Hydrolysis of alpha-(2->3)-, alpha-(2->6)-, alpha-(2->8)- glycosidic linkages of terminal sialic residues in oligosaccharides, glycoproteins, glycolipids, colominic acid and synthetic substrates. |
| post-translat. modifications | N-glycosylated (by similarity). |
| subcellular loc. | Preferentially accumulates at the apical plasma membrane in infected polarized epithelial cells, which is the virus assembly site. Uses lipid rafts for cell surface transport and apical sorting. Type ii membrane protein. In the virion, forms a mushroom-shaped spike on the surface of the membrane (by similarity). |
| enzyme regulation | These drugs interfere with the release of progeny virus from infected cells and are effective against all influenza strains. Inhibited by the neuraminidase inhibitors zanamivir (relenza) and oseltamivir (tamiflu). Resistance to neuraminidase inhibitors is quite rare. |
| Gene | IGH-1A (M. musculus); NA (M. musculus) |
| function | Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. May facilitate viral invasion of the upper airways by cleaving the sialic acid moities on the mucin of the airway epithelial cells. Described as a receptor-destroying enzyme because it cleaves a terminal sialic acid from the cellular receptors. Otherwise, infection would be limited to one round of replication. Cleaves off the terminal sialic acids on the glycosylated ha during virus budding to facilitate virus release. Likely to plays a role in the budding process through its association with lipid rafts during intracellular transport. Additionally helps virus spread through the circulation by further removing sialic acids from the cell surface. These cleavages prevent self-aggregation and ensure the efficient spread of the progeny virus from cell to cell. Plays a role in the determination of host range restriction on replication and virulence. Sialidase activity in late endosome/lysosome traffic seems to enhance virus replication. May additionally display a raft-association independent effect on budding. |
Gene
Ontology | |
| Primary reference | Crystal structures of two mutant neuraminidase-antibody complexes with amino acid substitutions in the interface., Tulip WR, Varghese JN, Webster RG, Laver WG, Colman PM, J Mol Biol 1992 Sep 5;227(1):149-59. PMID:1522584 |
