1F8D	Hydrolase Hydrolase Inhibitor	date	Jun 30, 2000
title	Native Influenza Neuraminidase In Complex With 9-Amino-2- Deoxy-2,3-Dehydro-N-Neuraminic Acid
authors	B.J.Smith, P.M.Colman, M.Von Itzstein, B.Danylec, J.N.Varghese
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 Engineered: Yes		Organism_scientific: Influenza A Virus (Aternaustraliag70c1975(H11n9)); Organism_taxid: 384509 Strain: Aternaustraliag70c75 Expression_system: Influenza A Virus Expression_system_taxid: 11320 Expression_system_strain: Recombinant (Nwsg70c) N9
symmetry	Space Group: I 4 3 2	R_factor 0.201 R_Free 0.231
crystal cell	length a length b length c angle alpha angle beta angle gamma 180.740 180.740 180.740 90.00 90.00 90.00
method	X-Ray Diffraction	resolution	1 Å
ligand	9AM, 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: 1F8E, 2QWC
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.
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	Analysis of inhibitor binding in influenza virus neuraminidase., Smith BJ, Colman PM, Von Itzstein M, Danylec B, Varghese JN, Protein Sci 2001 Apr;10(4):689-96. PMID:11274459

Data retrieval

Asymmetric unit, PDB entry: [header only] [complete with coordinates] (79 Kb) [Save to disk] Biological Unit Coordinates (1f8d.pdb1.gz) 284 Kb CSU: Contacts of Structural Units for 1F8D Likely Quarternary Molecular Structure file(s) for 1F8D Structure Factors (617 Kb) Retrieve 1F8D in mmCIF format [Save to disk]

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Structure-derived information

Conformational Epitope Prediction for 1F8D from the CEP Server. Electron Density related parameters from EDS Electron Density Server, at Upsala Dipole moment, from Dipole Server at Weizmann Institute Crystal Contacts, from CryCo at Weizmann Institute 3D motif for 1F8D, from MSDmotif at EBI Classification of representative domains in scop (Structural Classification of Proteins)     - Domain d1f8da_, region A [Jmol] [rasmolscript] [script source] Fold representative 1f8d 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: [1f8d_A]

Other resources with information on 1F8D

InterPro: IPR001860 MMDB (Entrez's Structure Database)

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