2QWF	Hydrolase	date	Apr 07, 1998
title	The X-Ray Structure Of A Complex Of N-Acetyl-4-Guanidino-6- Methyl(Propyl)Carboxamide-4,5-Dihydro-2h-Pyran-2- Carboxylic Acid 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 0.167 R_Free NULL
crystal cell	length a length b length c angle alpha angle beta angle gamma 181.410 181.410 181.410 90.00 90.00 90.00
method	X-Ray Diffraction	resolution	1 Å
ligand	BMA, CA, G20, MAN, NAG	enzyme	Exo-alpha-sialidase;. Neuraminidase;. Sialidase;. Alpha-neuraminidase;. Acetylneuraminidase. Hydrolase E.C.3.2.1.18 BRENDA
related structures	by homologous chain: 1L7G, 2QWE
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	Chain Function Process Component 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 reference	Drug 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

Asymmetric unit, PDB entry: [header only] [complete with coordinates] (81 Kb) [Save to disk] Biological Unit Coordinates (2qwf.pdb1.gz) 288 Kb CSU: Contacts of Structural Units for 2QWF Likely Quarternary Molecular Structure file(s) for 2QWF Retrieve 2QWF in mmCIF format [Save to disk]

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Structure-derived information

Dipole moment, from Dipole Server at Weizmann Institute Crystal Contacts, from CryCo at Weizmann Institute 3D motif for 2QWF, from MSDmotif at EBI Classification of representative domains in scop (Structural Classification of Proteins)     - Domain d2qwf__, region [Jmol] [rasmolscript] [script source] Fold representative 2qwf from FSSP and Dali (Families of Structurally Similar Proteins) Class (fold), Architecture (subfold), Topology, Homologous superfamily from CATH Summaries and structural analyses of PDB data files from PDBSum Identification of Protein Pockets & Cavities at CASTp

Sequence-derived information

View one-letter amino acid or nucleotide sequence for each chain: [2qwf_A]

Other resources with information on 2QWF

InterPro: IPR001860 MMDB (Entrez's Structure Database)

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