PDBsum entry 1ncd

Hydrolase(o-glycosyl)

PDB id: 1ncd

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 neuraminidase-nc41 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

Protein chain

P05803  (NRAM_I84A1) -  Neuraminidase from Influenza A virus (strain A/Whale/Maine/1/1984 H13N9)

Seq: 470 a.a.

Struc: 389 a.a.*

Protein chain

No UniProt id for this chain

Struc: 214 a.a.

Protein chain

P01865  (GCAM_MOUSE) -  Immunoglobulin heavy constant gamma 2A from Mus musculus

Seq: 398 a.a.

Struc: 221 a.a.

* 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.
• 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)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.