PDBsum entry 1nca

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Hydrolase(o-glycosyl) PDB id
Protein chains
389 a.a. *
214 a.a. *
221 a.a. *
NAG ×2
Waters ×72
* Residue conservation analysis

References listed in PDB file
Key reference
Title Refined crystal structure of the influenza virus n9 neuraminidase-Nc41 FAB complex.
Authors W.R.Tulip, J.N.Varghese, W.G.Laver, R.G.Webster, P.M.Colman.
Ref. J Mol Biol, 1992, 227, 122-148. [DOI no: 10.1016/0022-2836(92)90687-F]
PubMed id 1381757
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)
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.
Secondary reference #1
Title Crystal structures of two mutant neuraminidase-Antibody complexes with amino acid substitutions in the interface.
Authors W.R.Tulip, J.N.Varghese, R.G.Webster, W.G.Laver, P.M.Colman.
Ref. J Mol Biol, 1992, 227, 149-159. [DOI no: 10.1016/0022-2836(92)90688-G]
PubMed id 1522584
Full text Abstract
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 reproduced from the cited reference with permission from Elsevier
Secondary reference #2
Title Crystal structures of neuraminidase-Antibody complexes.
Authors W.R.Tulip, J.N.Varghese, R.G.Webster, G.M.Air, W.G.Laver, P.M.Colman.
Ref. Cold Spring Harb Symp Quant Biol, 1989, 54, 257-263.
PubMed id 2484162
Secondary reference #3
Title Three-Dimensional structure of a complex of antibody with influenza virus neuraminidase.
Authors P.M.Colman, W.G.Laver, J.N.Varghese, A.T.Baker, P.A.Tulloch, G.M.Air, R.G.Webster.
Ref. Nature, 1987, 326, 358-363.
PubMed id 2436051
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