1A14	Complex (Antibody Antigen)	date	Dec 21, 1997
title	Complex Between Nc10 Anti-Influenza Virus Neuraminidase Single Chain Antibody With A 5 Residue Linker And Influenza Virus Neuraminidase
authors	R.L.Malby, A.J.Mccoy, A.A.Kortt, P.J.Hudson, P.M.Colman
compound		source
Molecule: Neuraminidase Chain: N Fragment: Residues 82 - 468 Ec: 3.2.1.18		Organism_scientific: Influenza A Virus Organism_taxid: 11320 Strain: N9, Aternaustraliag70c75
Molecule: Nc10 Fv (Heavy Chain) Chain: H Fragment: Vh Domain Of Anti-Neuraminidase Antibody Nc10 Covalently Joined By A Five-Residue Polypeptide Linker; Engineered: Yes		Organism_scientific: Mus Musculus Organism_common: House Mouse Organism_taxid: 10090 Expression_system: Escherichia Coli Expression_system_taxid: 562
Molecule: Nc10 Fv (Light Chain) Chain: L Fragment: Vl Domain Of Anti-Neuraminidase Antibody Nc10 Covalently Joined By A Five-Residue Polypeptide Linker; Engineered: Yes		Organism_scientific: Mus Musculus Organism_common: House Mouse Organism_taxid: 10090 Expression_system: Escherichia Coli Expression_system_taxid: 562
symmetry	Space Group: I 4 2 2	R_factor 0.200 R_Free 0.270
crystal cell	length a length b length c angle alpha angle beta angle gamma 165.300 165.300 182.400 90.00 90.00 90.00
method	X-Ray Diffraction	resolution	2 Å
ligand	BMA, CA, MAN, NAG, NDG	enzyme	Exo-alpha-sialidase;. Neuraminidase;. Sialidase;. Alpha-neuraminidase;. Acetylneuraminidase. Hydrolase E.C.3.2.1.18 BRENDA
related structures	by homologous chain: 15C8, 1NMB, 1NNA, 2JEL
domain	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. The transmembrane domain also plays a role in lipid raft association (by similarity).
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. Type ii membrane protein. Uses lipid rafts for cell surface transport and apical sorting. 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. 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. Additionally helps virus spread through the circulation by further removing sialic acids from the cell surface. May additionally display a raft-association independent effect on budding.
Gene Ontology	Chain Function Process Component H, L antigen binding N 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	Three-dimensional structures of single-chain Fv-neuraminidase complexes., Malby RL, McCoy AJ, Kortt AA, Hudson PJ, Colman PM, J Mol Biol 1998 Jun 19;279(4):901-10. PMID:9642070

Data retrieval

Asymmetric unit, PDB entry: [header only] [complete with coordinates] (111 Kb) [Save to disk] Biological Unit Coordinates (1a14.pdb1.gz) 410 Kb CSU: Contacts of Structural Units for 1A14 Likely Quarternary Molecular Structure file(s) for 1A14 Retrieve 1A14 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 1A14, from MSDmotif at EBI Genome occurence of 1A14's fold from GeneCensus Classification of representative domains in scop (Structural Classification of Proteins)     - Domain d1a14h_, region H [Jmol] [rasmolscript] [script source]     - Domain d1a14l_, region L [Jmol] [rasmolscript] [script source]     - Domain d1a14n_, region N [Jmol] [rasmolscript] [script source] Fold representative 1a14 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: [1a14_H] [1a14_L] [1a14_N]

Other resources with information on 1A14

InterPro: IPR003596 , IPR007110 , IPR001860 MMDB (Entrez's Structure Database)

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