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PDBsum entry 1ncc
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Hydrolase(o-glycosyl)
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PDB id
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1ncc
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Contents |
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389 a.a.
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214 a.a.
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221 a.a.
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystal structures of two mutant neuraminidase-Antibody complexes with amino acid substitutions in the interface.
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Authors
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W.R.Tulip,
J.N.Varghese,
R.G.Webster,
W.G.Laver,
P.M.Colman.
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Ref.
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J Mol Biol, 1992,
227,
149-159.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Figure 1.
Figure 1. Data completeness versus resolution for the 2
mutant complexes, 1368R (crosses) and N329D
(triangles)
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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.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1992,
227,
149-159)
copyright 1992.
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Secondary reference #1
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Title
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Refined crystal structure of the influenza virus n9 neuraminidase-Nc41 FAB complex.
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Authors
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W.R.Tulip,
J.N.Varghese,
W.G.Laver,
R.G.Webster,
P.M.Colman.
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Ref.
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J Mol Biol, 1992,
227,
122-148.
[DOI no: ]
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PubMed id
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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.
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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.
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The above figures are
reproduced from the cited reference
with permission from Elsevier
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Secondary reference #2
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Title
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Crystal structures of neuraminidase-Antibody complexes.
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Authors
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W.R.Tulip,
J.N.Varghese,
R.G.Webster,
G.M.Air,
W.G.Laver,
P.M.Colman.
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Ref.
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Cold Spring Harb Symp Quant Biol, 1989,
54,
257-263.
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PubMed id
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Secondary reference #3
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Title
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Three-Dimensional structure of a complex of antibody with influenza virus neuraminidase.
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Authors
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P.M.Colman,
W.G.Laver,
J.N.Varghese,
A.T.Baker,
P.A.Tulloch,
G.M.Air,
R.G.Webster.
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Ref.
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Nature, 1987,
326,
358-363.
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PubMed id
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