1L7F Hydrolase date Mar 15, 2002
title Crystal Structure Of Influenza Virus Neuraminidase In Complex With Bcx-1812
authors B.J.Smith, J.L.Mckimm-Breshkin, M.Mcdonald, R.T.Fernley, J.N.Varghese, P.M.Colman
compound source
Molecule: Neuraminidase
Chain: A
Fragment: Integral Membrane Protein, Membrane Stalk Cleaved By Pronase Releasing Fully Active Residues 82-468;
Ec: 3.2.1.18
Organism_scientific: Influenza A Virus
Organism_taxid: 11320
Strain: Anwsternaustraliag70c75
symmetry Space Group: I 4 3 2
R_factor 0.153 R_Free 0.187
crystal
cell
length a length b length c angle alpha angle beta angle gamma
181.122 181.122 181.122 90.00 90.00 90.00
method X-Ray Diffractionresolution 1 Å
ligand BCZ, BMA, CA, GOL, MAN, NAG enzyme Exo-alpha-sialidase;. Neuraminidase;. Sialidase;. Alpha-neuraminidase;. Acetylneuraminidase. Hydrolase E.C.3.2.1.18 BRENDA
related structures by homologous chain: 1F8C, 1NNC
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 NA
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
ChainFunctionProcessComponent
A
  • exo-alpha-sialidase activity...
  • calcium ion binding
  • hydrolase activity
  • hydrolase activity, acting o...
  • metal ion binding
  • carbohydrate metabolic proce...
  • metabolic process
  • plasma membrane
  • membrane
  • integral to membrane
  • virion
  • host cell plasma membrane
  • virion membrane
  • Primary referenceStructural studies of the resistance of influenza virus neuramindase to inhibitors., Smith BJ, McKimm-Breshkin JL, McDonald M, Fernley RT, Varghese JN, Colman PM, J Med Chem 2002 May 23;45(11):2207-12. PMID:12014958
    Data retrieval
  • Asymmetric unit, PDB entry: [header only] [complete with coordinates] (86 Kb) [Save to disk]
  • Biological Unit Coordinates (1l7f.pdb1.gz) 311 Kb
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