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PDBsum entry 2aeq
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Hydrolase/immune system
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PDB id
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2aeq
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Contents |
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388 a.a.
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107 a.a.
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116 a.a.
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References listed in PDB file
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Key reference
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Title
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An epidemiologically significant epitope of a 1998 human influenza virus neuraminidase forms a highly hydrated interface in the na-Antibody complex.
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Authors
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L.Venkatramani,
E.Bochkareva,
J.T.Lee,
U.Gulati,
W.Graeme laver,
A.Bochkarev,
G.M.Air.
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Ref.
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J Mol Biol, 2006,
356,
651-663.
[DOI no: ]
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PubMed id
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Abstract
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The crystal structure of the complex between neuraminidase (NA) of influenza
virus A/Memphis/31/98 (H3N2) and Fab of monoclonal antibody Mem5 has been
determined at 2.1A resolution and shows a novel pattern of interactions compared
to other NA-Fab structures. The interface buries a large area of 2400A(2) and
the surfaces have high complementarity. However, the interface is also highly
hydrated. There are 33 water molecules in the interface >/=95% buried from bulk
solvent, but only 13 of these are isolated from other water molecules. The rest
are involved in an intricate network of water-mediated hydrogen bonds throughout
the interface, stabilizing the complex. Glu199 on NA, the most critical
side-chain to the interaction as previously determined by escape mutant analysis
and site-directed mutation, is located in a non-aqueous island. Glu199 and three
other residues that contribute the major part of the antigen buried surface of
the complex have mutated in human influenza viruses isolated after 1998,
confirming that Mem5 identifies an epidemiologically important antigenic site.
We conclude that antibody selection of NA variants is a significant component of
recent antigenic drift in human H3N2 influenza viruses, supporting the idea that
influenza vaccines should contain NA in addition to hemagglutinin.
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Figure 1.
Figure 1. Crystal structures of NA-Fab complexes showing
the different binding site in Mem/98 NA compared to N9 NA.
(a)-(c). The NA (brown) is shown in approximately the same
orientation in each panel. The antibody heavy chain is in blue,
the light chain is in mauve. N-linked carbohydrates are in
green; the long carbohydrate chain is attached to Asn200. The
view is looking parallel with the viral membrane, with the
Pronase cleavage site at the bottom. The stalk would continue
down the page to the viral membrane. (a) Stereo view of the
Mem/98 N2 NA-Mem5 Fab complex. Electron density was not
continuous for the constant domains of Mem5 Fab and only part of
those are included. A sulfate ion (red spheres) marks the active
site. (b) The N9 NA-NC41 Fab complex (PDB 1NCA). Only the Fv
domain of the antibody is shown. (c) N9 NA-NC10 Fab complex (PDB
1NMB). Contacts include the carbohydrate chain attached to
Asn200 of the adjacent subunit, so that chain is included in the
asymmetric unit. (d) Looking down on to the top surface of the
N9 NA tetramer (green) with four Fvs of NC10 bound. (e) The
Mem/98 NA tetramer with four Fvs of Mem5 bound. The images were
prepared using PyMol (DeLano Scientific).
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Figure 4.
Figure 4. Water molecules form an intricate network of
hydrogen-bonded water molecules across the interface and
water-mediated hydrogen bonds between the NA and Fab. (a) The
water network encircles Glu199. Broken lines are water-water
hydrogen bonds. (b) Schematic of the water interactions in the
interface. The water molecules are identified in magenta, NA
residues are green, antibody H chain residues are dark blue and
L chain residues are light blue. H-bonds are black lines. Direct
contacts between protein residues are shown by broken red lines
to give a sense of the spatial relationships.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2006,
356,
651-663)
copyright 2006.
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