spacer
spacer

PDBsum entry 1ncc
Go to PDB code: 
protein ligands metals Protein-protein interface(s) links
Hydrolase(o-glycosyl) PDB id
1ncc

 

 

 

 

Loading ...

 
JSmol PyMol  
Contents
Protein chains
389 a.a. *
214 a.a. *
221 a.a. *
Ligands
NAG-NAG-BMA-MAN-
MAN-MAN
NAG ×2
Metals
_CA
* Residue conservation analysis
PDB id:
1ncc
Name: Hydrolase(o-glycosyl)
Title: Crystal structures of two mutant neuraminidase-antibody complexes with amino acid substitutions in the interface
Structure: Influenza a subtype n9 neuraminidase. Chain: n. Igg2a-kappa nc41 fab (light chain). Chain: l. Igg2a-kappa nc41 fab (heavy chain). Chain: h
Source: Influenza a virus. Organism_taxid: 384509. Strain: (a/tern/australia/g70c/1975(h11n9)). Mus musculus. House mouse. Organism_taxid: 10090. Organism_taxid: 10090
Biol. unit: Dodecamer (from PQS)
Resolution:
2.50Å     R-factor:   0.212    
Authors: W.R.Tulip,J.N.Varghese,P.M.Colman
Key ref:
W.R.Tulip et al. (1992). Crystal structures of two mutant neuraminidase-antibody complexes with amino acid substitutions in the interface. J Mol Biol, 227, 149-159. PubMed id: 1522584 DOI: 10.1016/0022-2836(92)90688-G
Date:
21-Jan-92     Release date:   31-Jan-94    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P03472  (NRAM_I75A5) -  Neuraminidase from Influenza A virus (strain A/Tern/Australia/G70C/1975 H11N9)
Seq:
Struc: 		470 a.a.
389 a.a.*
Protein chain
No UniProt id for this chain
Struc: 214 a.a.
Protein chain
Pfam   ArchSchema ?
P01865  (GCAM_MOUSE) -  Immunoglobulin heavy constant gamma 2A from Mus musculus
Seq:
Struc: 		398 a.a.
221 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: Chain N: E.C.3.2.1.18  - 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.

 

 
DOI no: 10.1016/0022-2836(92)90688-G J Mol Biol 227:149-159 (1992)
PubMed id: 1522584  
 
 
Crystal structures of two mutant neuraminidase-antibody complexes with amino acid substitutions in the interface.
W.R.Tulip, J.N.Varghese, R.G.Webster, W.G.Laver, P.M.Colman.
 
  ABSTRACT  
 
The site on influenza virus N9 neuraminidase recognized by NC41 monoclonal antibody comprises 19 amino acid residues that are in direct contact with 17 residues on the antibody. Single sequence changes in some of the neuraminidase residues in the site markedly reduce antibody binding. However, two mutants have been found within the site, Ile368 to Arg and Asn329 to Asp selected by antibodies other than NC41, and these mutants bind NC41 antibody with only slightly reduced affinity. The three-dimensional structures of the two mutant N9-NC41 antibody complexes as derived from the wild-type complex are presented. Both structures show that some amino acid substitutions can be accommodated within an antigen-antibody interface by local structural rearrangements around the mutation site. In the Ile368 to Arg mutant complex, the side-chain of Arg368 is shifted by 2.9 A from its position in the uncomplexed mutant and a shift of 1.3 A in the position of the light chain residue HisL55 with respect to the wild-type complex is also observed. In the other mutant, the side-chain of Asp329 appears rotated by 150 degrees around C alpha-C beta with respect to the uncomplexed mutant, so that the carboxylate group is moved to the periphery of the antigen-antibody interface. The results provide a basis for understanding some of the potential structural effects of somatic hypermutation on antigen-antibody binding in those cases where the mutation in the antibody occurs at antigen-contacting residues, and demonstrate again the importance of structural context in evaluating the effect of amino acid substitutions on protein structure and function.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Data completeness versus resolution for the 2 mutant complexes, 1368R (crosses) and N329D (triangles) 		Figure 2.
Figure 2. (a) Difference map using wild-type phases between 1368R and wild-type C41 complexes overlaid ith the final models of mutant (yellow) and wild-type (blue). Solid and broken contours are at +4a and -4a espectively. (b) 2F,-Fc map conoured at 20 of the efined 1368R complex using phases from that structure including Arg368. Overlaid are the odels of the refined 1368R complex (yellow) and he refined uncomplexed 1368R mutant (red). Neuraminidase residue numbers are prefixed with N.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1992, 227, 149-159) copyright 1992.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19254207 P.M.Colman (2009).
New antivirals and drug resistance.
  Annu Rev Biochem, 78, 95.  
19457254 S.Maurer-Stroh, J.Ma, R.T.Lee, F.L.Sirota, and F.Eisenhaber (2009).
Mapping the sequence mutations of the 2009 H1N1 influenza A virus neuraminidase relative to drug and antibody binding sites.
  Biol Direct, 4, 18; discussion 18.  
18234071 V.Moreau, C.Fleury, D.Piquer, C.Nguyen, N.Novali, S.Villard, D.Laune, C.Granier, and F.Molina (2008).
PEPOP: computational design of immunogenic peptides.
  BMC Bioinformatics, 9, 71.  
17177888 B.Piekarska, A.Drozd, L.Konieczny, M.Król, W.Jurkowski, I.Roterman, P.Spólnik, B.Stopa, and J.Rybarska (2006).
The indirect generation of long-distance structural changes in antibodies upon their binding to antigen.
  Chem Biol Drug Des, 68, 276-283.  
16809065 N.S.Longo, and P.E.Lipsky (2006).
Why do B cells mutate their immunoglobulin receptors?
  Trends Immunol, 27, 374-380.  
15858274 G.H.Cohen, E.W.Silverton, E.A.Padlan, F.Dyda, J.A.Wibbenmeyer, R.C.Willson, and D.R.Davies (2005).
Water molecules in the antibody-antigen interface of the structure of the Fab HyHEL-5-lysozyme complex at 1.7 A resolution: comparison with results from isothermal titration calorimetry.
  Acta Crystallogr D Biol Crystallogr, 61, 628-633.
PDB code: 1yqv
12767122 M.Król, I.Roterman, B.Piekarska, L.Konieczny, J.Rybarska, and B.Stopa (2003).
Local and long-range structural effects caused by the removal of the N-terminal polypeptide fragment from immunoglobulin L chain lambda.
  Biopolymers, 69, 189-200.  
12414967 U.Gulati, C.C.Hwang, L.Venkatramani, S.Gulati, S.J.Stray, J.T.Lee, W.G.Laver, A.Bochkarev, A.Zlotnick, and G.M.Air (2002).
Antibody epitopes on the neuraminidase of a recent H3N2 influenza virus (A/Memphis/31/98).
  J Virol, 76, 12274-12280.  
10899782 D.Fleury, R.S.Daniels, J.J.Skehel, M.Knossow, and T.Bizebard (2000).
Structural evidence for recognition of a single epitope by two distinct antibodies.
  Proteins, 40, 572-578.
PDB code: 1eo8
10398393 Z.C.Fan, L.Shan, B.Z.Goldsteen, L.W.Guddat, A.Thakur, N.F.Landolfi, M.S.Co, M.Vasquez, C.Queen, P.A.Ramsland, and A.B.Edmundson (1999).
Comparison of the three-dimensional structures of a humanized and a chimeric Fab of an anti-gamma-interferon antibody.
  J Mol Recognit, 12, 19-32.
PDB codes: 1b2w 1b4j
9600924 B.Vallone, A.E.Miele, P.Vecchini, E.Chiancone, and M.Brunori (1998).
Free energy of burying hydrophobic residues in the interface between protein subunits.
  Proc Natl Acad Sci U S A, 95, 6103-6107.  
9602363 K.Andersson, J.Wrammert, and T.Leanderson (1998).
Affinity selection and repertoire shift: paradoxes as a consequence of somatic mutation?
  Immunol Rev, 162, 173-182.  
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.  
9609690 W.Dall'Acqua, E.R.Goldman, W.Lin, C.Teng, D.Tsuchiya, H.Li, X.Ysern, B.C.Braden, Y.Li, S.J.Smith-Gill, and R.A.Mariuzza (1998).
A mutational analysis of binding interactions in an antigen-antibody protein-protein complex.
  Biochemistry, 37, 7981-7991.
PDB code: 1a2y
9379075 K.D.Smith, Z.B.Kurago, and C.T.Lutz (1997).
Conformational changes in MHC class I molecules. Antibody, T-cell receptor, and NK cell recognition in an HLA-B7 model system.
  Immunol Res, 16, 243-259.  
9235220 P.M.Colman (1997).
Virus versus antibody.
  Structure, 5, 591-593.  
8952503 B.A.Fields, F.A.Goldbaum, W.Dall'Acqua, E.L.Malchiodi, A.Cauerhff, F.P.Schwarz, X.Ysern, R.J.Poljak, and R.A.Mariuzza (1996).
Hydrogen bonding and solvent structure in an antigen-antibody interface. Crystal structures and thermodynamic characterization of three Fv mutants complexed with lysozyme.
  Biochemistry, 35, 15494-15503.
PDB codes: 1kip 1kiq 1kir
8552677 D.R.Davies, and G.H.Cohen (1996).
Interactions of protein antigens with antibodies.
  Proc Natl Acad Sci U S A, 93, 7.  
8880929 S.Chacko, E.W.Silverton, S.J.Smith-Gill, D.R.Davies, K.A.Shick, K.A.Xavier, R.C.Willson, P.D.Jeffrey, C.Y.Chang, L.C.Sieker, and S.Sheriff (1996).
Refined structures of bobwhite quail lysozyme uncomplexed and complexed with the HyHEL-5 Fab fragment.
  Proteins, 26, 55-65.
PDB codes: 1bql 1dkj 1dkk
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.  
8878390 Y.Y.Li, K.D.Smith, Y.Shi, and C.T.Lutz (1996).
Alloreactive anti-HLA-B7 cytolytic T cell clones use restricted T cell receptor genes.
  Transplantation, 62, 954-961.  
  7613476 J.E.Van Eyk, R.A.Caday-Malcolm, L.Yu, R.T.Irvin, and R.S.Hodges (1995).
Anti-peptide monoclonal antibody imaging of a common binding domain involved in muscle regulation.
  Protein Sci, 4, 781-790.  
  7537661 N.Verdaguer, M.G.Mateu, D.Andreu, E.Giralt, E.Domingo, and I.Fita (1995).
Structure of the major antigenic loop of foot-and-mouth disease virus complexed with a neutralizing antibody: direct involvement of the Arg-Gly-Asp motif in the interaction.
  EMBO J, 14, 1690-1696.  
  7613462 S.C.Bagley, and R.B.Altman (1995).
Characterizing the microenvironment surrounding protein sites.
  Protein Sci, 4, 622-635.  
7511810 J.Cherfils, T.Bizebard, M.Knossow, and J.Janin (1994).
Rigid-body docking with mutant constraints of influenza hemagglutinin with antibody HC19.
  Proteins, 18, 8.  
  7849585 P.M.Colman (1994).
Influenza virus neuraminidase: structure, antibodies, and inhibitors.
  Protein Sci, 3, 1687-1696.  
7994573 R.L.Malby, W.R.Tulip, V.R.Harley, J.L.McKimm-Breschkin, W.G.Laver, R.G.Webster, and P.M.Colman (1994).
The structure of a complex between the NC10 antibody and influenza virus neuraminidase and comparison with the overlapping binding site of the NC41 antibody.
  Structure, 2, 733-746.
PDB code: 1nmb
7680132 J.M.Nuss, P.B.Whitaker, and G.M.Air (1993).
Identification of critical contact residues in the NC41 epitope of a subtype N9 influenza virus neuraminidase.
  Proteins, 15, 121-132.  
8452674 R.A.Mariuzza, and R.J.Poljak (1993).
The basics of binding: mechanisms of antigen recognition and mimicry by antibodies.
  Curr Opin Immunol, 5, 50-55.  
8356074 V.Chitarra, P.M.Alzari, G.A.Bentley, T.N.Bhat, J.L.Eiselé, A.Houdusse, J.Lescar, H.Souchon, and R.J.Poljak (1993).
Three-dimensional structure of a heteroclitic antigen-antibody cross-reaction complex.
  Proc Natl Acad Sci U S A, 90, 7711-7715.
PDB codes: 1jhl 2ihl
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. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

spacer
spacer