PDBsum entry 1nma

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protein ligands Protein-protein interface(s) links
Complex (hydrolase/immunoglobulin) PDB id
Protein chains
378 a.a. *
109 a.a. *
122 a.a. *
* Residue conservation analysis
PDB id:
Name: Complex (hydrolase/immunoglobulin)
Title: N9 neuraminidase complexes with antibodies nc41 and nc10: em free-energy calculations capture specificity trends observe mutant binding data
Structure: N9 neuraminidase. Chain: n. Mutation: yes. Fab nc10. Chain: l. Other_details: resolution of 3.0 angstroms. Fab nc10. Chain: h. Other_details: resolution of 3.0 angstroms
Source: Influenza a virus. Organism_taxid: 11320. Mus musculus. House mouse. Organism_taxid: 10090. Other_details: isolated from monoclonal murine antibody. Other_details: isolated from monoclonal murine antibody
Biol. unit: Dodecamer (from PQS)
3.00Å     R-factor:   0.200    
Authors: W.R.Tulip,J.N.Varghese,P.M.Colman
Key ref:
W.R.Tulip et al. (1994). N9 neuraminidase complexes with antibodies NC41 and NC10: empirical free energy calculations capture specificity trends observed with mutant binding data. Biochemistry, 33, 7986-7997. PubMed id: 7517697 DOI: 10.1021/bi00192a002
06-May-94     Release date:   15-Sep-95    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P05803  (NRAM_I84A1) -  Neuraminidase
470 a.a.
378 a.a.*
Protein chain
No UniProt id for this chain
Struc: 109 a.a.
Protein chain
No UniProt id for this chain
Struc: 122 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chain N: E.C.  - Exo-alpha-sialidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 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.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   3 terms 
  Biological process     carbohydrate metabolic process   1 term 
  Biochemical function     exo-alpha-sialidase activity     1 term  


DOI no: 10.1021/bi00192a002 Biochemistry 33:7986-7997 (1994)
PubMed id: 7517697  
N9 neuraminidase complexes with antibodies NC41 and NC10: empirical free energy calculations capture specificity trends observed with mutant binding data.
W.R.Tulip, V.R.Harley, R.G.Webster, J.Novotny.
X-ray crystallographic coordinates of influenza virus N9 neuraminidase complexed with monoclonal antibodies NC41 and NC10 [Tulip et al. (1992) J. Mol. Biol. 227, 122-148] served as a starting point for calculations aimed at estimating free energy changes (delta G) of complex formation between the two antibodies and the neuraminidase. Using an empirical function incorporating hydrophobic, electrostatic, and conformational entropy effects, we estimated contributions individual neuraminidase residues make to complex formation (delta G(residue)) and compared the calculated values to experimentally measured differences in antibody binding between the wild-type and mutated neuraminidases [Nuss et al. (1993) Proteins 15, 121-132; calculations done without prior knowledge of the experimental data]. A good correspondence was found between the calculated delta G(residue) values and the mutant binding data in that side chains with large calculated delta G contributions (delta G(residue) < -1 kcal/mol) lie at sites of mutation which cause a marked reduction in antibody binding, and side chains for which delta G(residue) > -1 kcal/mol are sites at which a mutation does not have a marked effect on binding. Because most of the delta G(residue) < -1 kcal/mol side chains also make hydrogen bonds/salt bridges with the antibody, the correspondence of the effect of antibody binding with these electrostatic interactions (18 out of 27 for NC41 and, tentatively, 5 out of 7 for NC10) is about as good as that with predicted energetic residues. All the delta G(residue) < -1 kcal/mol neuraminidase side chains cluster around the most protruding surface regions and are thus spread over different epitope segments. Surprisingly, different residues were found to make the most critical contributions to the NC41 and NC10 complex stabilities despite the fact that the NC41 and NC10 antigenic epitopes overlap, having approximately 70% of surface residues in common. It is thus possible, for two different antibodies, to recognize the same protein surface in strikingly different ways. As only a fraction of the neuraminidase residues appear to make large contributions to antibody binding, the results also support the hypothesis of a "functional" epitope in antigen-antibody interactions. Positive trends between both backbone rigidity and residue accessibility in the complexed state, and contributions of these residues to binding, were also observed for the NC41 complex.

Literature references that cite this PDB file's key reference

  PubMed id Reference
  20025194 J.L.Cherry, D.J.Lipman, A.Nikolskaya, and Y.I.Wolf (2009).
Evolutionary dynamics of N-glycosylation sites of influenza virus hemagglutinin.
  PLoS Curr, 1, RRN1001.  
16251186 M.J.Clément, A.Fortuné, A.Phalipon, V.Marcel-Peyre, C.Simenel, A.Imberty, M.Delepierre, and L.A.Mulard (2006).
Toward a better understanding of the basis of the molecular mimicry of polysaccharide antigens by peptides: the example of Shigella flexneri 5a.
  J Biol Chem, 281, 2317-2332.  
15162489 S.Liu, C.Zhang, H.Zhou, and Y.Zhou (2004).
A physical reference state unifies the structure-derived potential of mean force for protein folding and binding.
  Proteins, 56, 93.  
11807947 L.Jiang, Y.Gao, F.Mao, Z.Liu, and L.Lai (2002).
Potential of mean force for protein-protein interaction studies.
  Proteins, 46, 190-196.  
10677211 J.C.Burnett, G.E.Kellogg, and D.J.Abraham (2000).
Computational methodology for estimating changes in free energies of biomolecular association upon mutation. The importance of bound water in dimer-tetramer assembly for beta 37 mutant hemoglobins.
  Biochemistry, 39, 1622-1633.  
10451557 B.Selisko, A.F.Licea, B.Becerril, F.Zamudio, L.D.Possani, and E.Horjales (1999).
Antibody BCF2 against scorpion toxin Cn2 from Centuroides noxius Hoffmann: primary structure and three-dimensional model as free Fv fragment and complexed with its antigen.
  Proteins, 37, 130-143.  
10480891 J.A.Wibbenmeyer, P.Schuck, S.J.Smith-Gill, and R.C.Willson (1999).
Salt links dominate affinity of antibody HyHEL-5 for lysozyme through enthalpic contributions.
  J Biol Chem, 274, 26838-26842.  
10398408 M.Schapira, M.Totrov, and R.Abagyan (1999).
Prediction of the binding energy for small molecules, peptides and proteins.
  J Mol Recognit, 12, 177-190.  
9700501 B.C.Braden, E.R.Goldman, R.A.Mariuzza, and R.J.Poljak (1998).
Anatomy of an antibody molecule: structure, kinetics, thermodynamics and mutational studies of the antilysozyme antibody D1.3.
  Immunol Rev, 163, 45-57.  
9692956 P.S.Pruett, and G.M.Air (1998).
Critical interactions in binding antibody NC41 to influenza N9 neuraminidase: amino acid contacts on the antibody heavy chain.
  Biochemistry, 37, 10660-10670.  
9235220 P.M.Colman (1997).
Virus versus antibody.
  Structure, 5, 591-593.  
8728658 P.Bamborough, and F.E.Cohen (1996).
Modeling protein-ligand complexes.
  Curr Opin Struct Biol, 6, 236-241.  
8703938 W.Dall'Acqua, E.R.Goldman, E.Eisenstein, and R.A.Mariuzza (1996).
A mutational analysis of the binding of two different proteins to the same antibody.
  Biochemistry, 35, 9667-9676.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.