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PDBsum entry 1ncd

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protein ligands metals Protein-protein interface(s) links
Hydrolase(o-glycosyl) PDB id
1ncd
Jmol PyMol
Contents
Protein chains
389 a.a. *
214 a.a. *
221 a.a. *
Ligands
NAG-NAG-BMA-MAN-
MAN-MAN
NAG
NAG-NAG
Metals
_CA
Waters ×69
* Residue conservation analysis
PDB id:
1ncd
Name: Hydrolase(o-glycosyl)
Title: Refined crystal structure of the influenza virus n9 neuramin fab complex
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: 11484. Strain: (a/whale/maine/1/84(h13n9)). Mus musculus. House mouse. Organism_taxid: 10090. Organism_taxid: 10090
Biol. unit: Dodecamer (from PQS)
Resolution:
2.90Å     R-factor:   0.157    
Authors: W.R.Tulip,J.N.Varghese,P.M.Colman
Key ref:
W.R.Tulip et al. (1992). Refined crystal structure of the influenza virus N9 neuraminidase-NC41 Fab complex. J Mol Biol, 227, 122-148. PubMed id: 1381757 DOI: 10.1016/0022-2836(92)90687-F
Date:
21-Jan-92     Release date:   31-Jan-94    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P05803  (NRAM_I84A1) -  Neuraminidase
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) -  Ig gamma-2A chain C region, membrane-bound form
Seq:
Struc:
398 a.a.
221 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   3 terms 
  Biological process     carbohydrate metabolic process   2 terms 
  Biochemical function     exo-alpha-sialidase activity     1 term  

 

 
DOI no: 10.1016/0022-2836(92)90687-F J Mol Biol 227:122-148 (1992)
PubMed id: 1381757  
 
 
Refined crystal structure of the influenza virus N9 neuraminidase-NC41 Fab complex.
W.R.Tulip, J.N.Varghese, W.G.Laver, R.G.Webster, P.M.Colman.
 
  ABSTRACT  
 
The crystal structure of the complex between neuraminidase from influenza virus (subtype N9 and isolated from an avian source) and the antigen-binding fragment (Fab) of monoclonal antibody NC41 has been refined by both least-squares and simulated annealing methods to an R-factor of 0.191 using 31,846 diffraction data in the resolution range 8.0 to 2.5 A. The resulting model has a root-mean-square deviation from ideal bond-length of 0.016 A. One fourth of the tetrameric complex comprises the crystallographic model, which has 6577 non-hydrogen atoms and consists of 389 protein residues and eight carbohydrate residues in the neuraminidase, 214 residues in the Fab light chain, and 221 residues in the heavy chain. One putative Ca ion buried in the neuraminidase, and 73 water molecules, are also included. A remarkable shape complementarity exists between the interacting surfaces of the antigen and the antibody, although the packing density of atoms at the interface is somewhat looser than in the interior of a protein. Similarly, there is a high degree of chemical complementarity between the antigen and antibody, mediated by one buried salt-link, two solvated salt-links and 12 hydrogen bonds. The antibody-binding site on neuraminidase is discontinuous and comprises five chain segments and 19 residues in contact, whilst 33 neuraminidase residues in eight segments have 899 A2 of surface area buried by the interaction (to a 1.7 A probe), including two hexose units. Seventeen residues in NC41 Fab lying in five of the six complementarity determining regions (CDRs) make contact with the neuraminidase and 36 antibody residues in seven segments have 916 A2 of buried surface area. The interface is more extensive than those of the three lysozyme-Fab complexes whose crystal structures have been determined, as judged by buried surface area and numbers of contact residues. There are only small differences (less than 1.5 A) between the complexed and uncomplexed neuraminidase structures and, at this resolution and accuracy, those differences are not unequivocal. The main-chain conformations of five of the CDRs follow the predicted canonical structures. The interface between the variable domains of the light and heavy chains is not as extensive as in other Fabs, due to less CDR-CDR interaction in NC41. The first CDR on the NC41 Fab light chain is positioned so that it could sterically hinder the approach of small as well as large substrates to the neuraminidase active-site pocket, suggesting a possible mechanism for the observed inhibition of enzyme activity by the antibody.(ABSTRACT TRUNCATED AT 400 WORDS)
 
  Selected figure(s)  
 
Figure 6.
Figure 6. c'' trace of the tetrameric complex between N9 neuraminidase (yellow) and the 4 NC41 Fabs (heavy chains ed, light chains blue and CDRs green) with the 4-fold axis approximately vertical. An asymmetric unit contains only one fo&th of the tetramer.
Figure 8.
Figure 8. The epitope region of neuraminidase in the tern E9%NC41 Fab complex (green) is shown with the corresponding residues from the uncomplexed N9 struc- ture overlaid (pink). Yellow labels are laced on resiues that may have different conformations in the 2 structures as judged by eletron-density maps. None of these differ- ences is unequivocal.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1992, 227, 122-148) copyright 1992.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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PDB codes: 3b7e 3beq
17177888 B.Piekarska, A.Drozd, L.Konieczny, M.Król, W.Jurkowski, I.Roterman, P.Spólnik, B.Stopa, and J.Rybarska (2006).
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Monoclonal antibodies to molluskan hemocyanin from Concholepas concholepas demonstrate common and specific epitopes among subunits.
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11707437 J.Valjakka, K.Takkinenz, T.Teerinen, H.Söderlund, and J.Rouvinen (2002).
Structural insights into steroid hormone binding: the crystal structure of a recombinant anti-testosterone Fab fragment in free and testosterone-bound forms.
  J Biol Chem, 277, 4183-4190.
PDB codes: 1i9i 1i9j
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).
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Electrostatic contributions to protein-protein interactions: fast energetic filters for docking and their physical basis.
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10709784 B.Tchernychev, A.Rabinkov, T.Miron, and M.Wilchek (2000).
Natural antibodies against alliinase in human serum and polyclonal antibodies elicited in rabbit share the same immunogenic determinants.
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10737939 D.W.Ritchie, and G.J.Kemp (2000).
Protein docking using spherical polar Fourier correlations.
  Proteins, 39, 178-194.  
10992290 M.T.Hearn, and P.T.Gomme (2000).
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  J Mol Recognit, 13, 223-278.  
11114068 R.H.Meloen, W.C.Puijk, and J.W.Slootstra (2000).
Mimotopes: realization of an unlikely concept.
  J Mol Recognit, 13, 352-359.  
11093161 S.N.Seal, M.Monestier, and M.Z.Radic (2000).
Diverse roles for the third complementarity determining region of the heavy chain (H3) in the binding of immunoglobulin Fv fragments to DNA, nucleosomes and cardiolipin.
  Eur J Immunol, 30, 3432-3440.  
  10211822 A.J.Jesaitis, D.Gizachew, E.A.Dratz, D.W.Siemsen, K.C.Stone, and J.B.Burritt (1999).
Actin surface structure revealed by antibody imprints: evaluation of phage-display analysis of anti-actin antibodies.
  Protein Sci, 8, 760-770.  
10488102 H.Kondo, M.Shiroishi, M.Matsushima, K.Tsumoto, and I.Kumagai (1999).
Crystal structure of anti-Hen egg white lysozyme antibody (HyHEL-10) Fv-antigen complex. Local structural changes in the protein antigen and water-mediated interactions of Fv-antigen and light chain-heavy chain interfaces.
  J Biol Chem, 274, 27623-27631.
PDB code: 1c08
10358765 H.Li, A.Llera, E.L.Malchiodi, and R.A.Mariuzza (1999).
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  Annu Rev Immunol, 17, 435-466.  
9927513 J.Thatte, A.Qadri, C.Radu, and E.S.Ward (1999).
Molecular requirements for T cell recognition by a major histocompatibility complex class II-restricted T cell receptor: the involvement of the fourth hypervariable loop of the Valpha domain.
  J Exp Med, 189, 509-520.  
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
9881971 H.Li, A.Llera, D.Tsuchiya, L.Leder, X.Ysern, P.M.Schlievert, K.Karjalainen, and R.A.Mariuzza (1998).
Three-dimensional structure of the complex between a T cell receptor beta chain and the superantigen staphylococcal enterotoxin B.
  Immunity, 9, 807-816.
PDB code: 1sbb
9628472 X.Ysern, H.Li, and R.A.Mariuzza (1998).
Imperfect interfaces.
  Nat Struct Biol, 5, 412-414.  
9145108 A.L.Corper, M.K.Sohi, V.R.Bonagura, M.Steinitz, R.Jefferis, A.Feinstein, D.Beale, M.J.Taussig, and B.J.Sutton (1997).
Structure of human IgM rheumatoid factor Fab bound to its autoantigen IgG Fc reveals a novel topology of antibody-antigen interaction.
  Nat Struct Biol, 4, 374-381.
PDB code: 1adq
9261086 C.H.Trinh, S.D.Hemmington, M.E.Verhoeyen, and S.E.Phillips (1997).
Antibody fragment Fv4155 bound to two closely related steroid hormones: the structural basis of fine specificity.
  Structure, 5, 937-948.
PDB codes: 1bfv 1cfv 2bfv
9434905 I.A.Wilson, and K.C.Garcia (1997).
T-cell receptor structure and TCR complexes.
  Curr Opin Struct Biol, 7, 839-848.  
9235220 P.M.Colman (1997).
Virus versus antibody.
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8880926 C.Tenette, F.Ducancel, and J.C.Smith (1996).
Structural model of the anti-snake-toxin antibody, M alpha 2,3.
  Proteins, 26, 9.  
8552677 D.R.Davies, and G.H.Cohen (1996).
Interactions of protein antigens with antibodies.
  Proc Natl Acad Sci U S A, 93, 7.  
8870072 P.Bork, A.K.Downing, B.Kieffer, and I.D.Campbell (1996).
Structure and distribution of modules in extracellular proteins.
  Q Rev Biophys, 29, 119-167.  
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
7576085 A.A.Kortt, R.E.Guthrie, M.G.Hinds, B.E.Power, N.Ivancic, J.B.Caldwell, L.C.Gruen, R.S.Norton, and P.J.Hudson (1995).
Solution properties of Escherichia coli-expressed VH domain of anti-neuraminidase antibody NC41.
  J Protein Chem, 14, 167-178.  
7716167 J.Janin (1995).
Elusive affinities.
  Proteins, 21, 30-39.  
7539913 K.P.Murphy, E.Freire, and Y.Paterson (1995).
Configurational effects in antibody-antigen interactions studied by microcalorimetry.
  Proteins, 21, 83-90.  
8747455 L.C.Kovari, C.Momany, and M.G.Rossmann (1995).
The use of antibody fragments for crystallization and structure determinations.
  Structure, 3, 1291-1293.  
  8575795 S.V.Kashmiri, L.Shu, E.A.Padlan, D.E.Milenic, J.Schlom, and P.H.Hand (1995).
Generation, characterization, and in vivo studies of humanized anticarcinoma antibody CC49.
  Hybridoma, 14, 461-473.  
8168505 A.A.Kortt, R.L.Malby, J.B.Caldwell, L.C.Gruen, N.Ivancic, M.C.Lawrence, G.J.Howlett, R.G.Webster, P.J.Hudson, and P.M.Colman (1994).
Recombinant anti-sialidase single-chain variable fragment antibody. Characterization, formation of dimer and higher-molecular-mass multimers and the solution of the crystal structure of the single-chain variable fragment/sialidase complex.
  Eur J Biochem, 221, 151-157.  
7529922 A.R.Friedman, V.A.Roberts, and J.A.Tainer (1994).
Predicting molecular interactions and inducible complementarity: fragment docking of Fab-peptide complexes.
  Proteins, 20, 15-24.  
7908437 C.Eigenbrot, T.Gonzalez, J.Mayeda, P.Carter, W.Werther, T.Hotaling, J.Fox, and J.Kessler (1994).
X-ray structures of fragments from binding and nonbinding versions of a humanized anti-CD18 antibody: structural indications of the key role of VH residues 59 to 65.
  Proteins, 18, 49-62.
PDB codes: 1fgv 2fgw
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.  
  8061604 J.F.Schildbach, S.Y.Shaw, R.E.Bruccoleri, E.Haber, L.A.Herzenberg, G.C.Jager, P.D.Jeffrey, D.J.Panka, D.R.Parks, and R.I.Near (1994).
Contribution of a single heavy chain residue to specificity of an anti-digoxin monoclonal antibody.
  Protein Sci, 3, 737-749.  
  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
  7756979 S.J.Hubbard, and P.Argos (1994).
Cavities and packing at protein interfaces.
  Protein Sci, 3, 2194-2206.  
8302837 T.N.Bhat, G.A.Bentley, G.Boulot, M.I.Greene, D.Tello, W.Dall'Acqua, H.Souchon, F.P.Schwarz, R.A.Mariuzza, and R.J.Poljak (1994).
Bound water molecules and conformational stabilization help mediate an antigen-antibody association.
  Proc Natl Acad Sci U S A, 91, 1089-1093.
PDB codes: 1vfa 1vfb
  7509002 T.Saito, G.Taylor, W.G.Laver, Y.Kawaoka, and R.G.Webster (1994).
Antigenicity of the N8 influenza A virus neuraminidase: existence of an epitope at the subunit interface of the neuraminidase.
  J Virol, 68, 1790-1796.  
7913750 V.C.Yee, L.C.Pedersen, I.Le Trong, P.D.Bishop, R.E.Stenkamp, and D.C.Teller (1994).
Three-dimensional structure of a transglutaminase: human blood coagulation factor XIII.
  Proc Natl Acad Sci U S A, 91, 7296-7300.
PDB code: 1ggt
7765190 W.C.Dougall, N.C.Peterson, and M.I.Greene (1994).
Antibody-structure-based design of pharmacological agents.
  Trends Biotechnol, 12, 372-379.  
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.  
8223570 L.C.Gruen, A.A.Kortt, and E.Nice (1993).
Determination of relative binding affinity of influenza virus N9 sialidases with the Fab fragment of monoclonal antibody NC41 using biosensor technology.
  Eur J Biochem, 217, 319-325.  
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.  
8497484 R.L.Malby, J.B.Caldwell, L.C.Gruen, V.R.Harley, N.Ivancic, A.A.Kortt, G.G.Lilley, B.E.Power, R.G.Webster, and P.M.Colman (1993).
Recombinant antineuraminidase single chain antibody: expression, characterization, and crystallization in complex with antigen.
  Proteins, 16, 57-63.  
8069628 R.L.Stanfield, M.Takimoto-Kamimura, J.M.Rini, A.T.Profy, and I.A.Wilson (1993).
Major antigen-induced domain rearrangements in an antibody.
  Structure, 1, 83-93.
PDB codes: 1ggb 1ggc
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 codes are shown on the right.

 

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