1XOG	Hydrolase	date	Oct 06, 2004
title	N9 Tern Influenza Neuraminidase Complexed With A 2,5- Disubstituted Tetrahydrofuran-5-Carboxylic Acid
authors	G.T.Wang, S.Wang, R.Gentles, T.Sowin, C.J.Maring, D.J.Kempf, W.M.Kati, V.Stoll, K.D.Stewart, G.Laver
compound		source
Molecule: Neuraminidase Chain: A Fragment: N9 Tern Neuraminidas Ec: 3.2.1.18		Organism_scientific: Influenza A Virus Organism_taxid: 11320 Strain: Strain Aternaustraliag70c75
symmetry	Space Group: I 4 3 2	R_factor 0.221 R_Free 0.297
crystal cell	length a length b length c angle alpha angle beta angle gamma 180.344 180.344 180.344 90.00 90.00 90.00
method	X-Ray Diffraction	resolution	2 Å
ligand	ABW, BMA, MAN, NAG	enzyme	Exo-alpha-sialidase;. Neuraminidase;. Sialidase;. Alpha-neuraminidase;. Acetylneuraminidase. Hydrolase E.C.3.2.1.18 BRENDA
related structures	by homologous chain: 1NCD, 1NNB
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	Design, synthesis, and structural analysis of inhibitors of influenza neuraminidase containing a 2,3-disubstituted tetrahydrofuran-5-carboxylic acid core., Wang GT, Wang S, Gentles R, Sowin T, Maring CJ, Kempf DJ, Kati WM, Stoll V, Stewart KD, Laver G, Bioorg Med Chem Lett 2005 Jan 3;15(1):125-8. PMID:15582424

Data retrieval

Asymmetric unit, PDB entry: [header only] [complete with coordinates] (67 Kb) [Save to disk] Biological Unit Coordinates (1xog.pdb1.gz) 61 Kb CSU: Contacts of Structural Units for 1XOG Likely Quarternary Molecular Structure file(s) for 1XOG Retrieve 1XOG 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 1XOG, from MSDmotif at EBI Classification of representative domains in scop (Structural Classification of Proteins)     - Domain d1xoga_, region A [Jmol] [rasmolscript] [script source] Fold representative 1xog from FSSP and Dali (Families of Structurally Similar Proteins)

Sequence-derived information

View one-letter amino acid or nucleotide sequence for each chain: [1xog_A]

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