2QWD Hydrolase date Apr 07, 1998
title The X-Ray Structure Of A Complex Of 4-Amino-Neu5ac2en And A Drug Resistant Variant R292k Of Tern N9 Influenza Virus Neuraminidase
authors J.N.Varghese
compound source
Molecule: Neuraminidase
Chain: A
Fragment: Residues 82 - 468
Synonym: Sialidase
Ec: 3.2.1.18
Mutation: Yes
Other_details: Integral Membrane Protein, Membrane Bound Stalk Cleaved By Pronase, Releasing Fully Active Head With Residues 82 - 468
Organism_scientific: Influenza A Virus
Organism_taxid: 11320
Strain: Aternaustraliag70c75
Variant: Neuraminidase R292k Mutation (N2-Tokyo367 Numbering)
symmetry Space Group: I 4 3 2
R_factor 0.165 R_Free NULL
crystal
cell
length a length b length c angle alpha angle beta angle gamma
180.900 180.900 180.900 90.00 90.00 90.00
method X-Ray Diffractionresolution 2 Å
ligand 4AM, 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: 1BJI, 2QWB
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 referenceDrug design against a shifting target: a structural basis for resistance to inhibitors in a variant of influenza virus neuraminidase., Varghese JN, Smith PW, Sollis SL, Blick TJ, Sahasrabudhe A, McKimm-Breschkin JL, Colman PM, Structure 1998 Jun 15;6(6):735-46. PMID:9655825
    Data retrieval
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  • Biological Unit Coordinates (2qwd.pdb1.gz) 287 Kb
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