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PDBsum entry 1e8v
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Contents |
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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 structure of the multifunctional paramyxovirus hemagglutinin-Neuraminidase.
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Authors
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S.Crennell,
T.Takimoto,
A.Portner,
G.Taylor.
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Ref.
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Nat Struct Biol, 2000,
7,
1068-1074.
[DOI no: ]
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PubMed id
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Abstract
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Paramyxoviruses are the main cause of respiratory disease in children. One of
two viral surface glycoproteins, the hemagglutinin-neuraminidase (HN), has
several functions in addition to being the major surface antigen that induces
neutralizing antibodies. Here we present the crystal structures of Newcastle
disease virus HN alone and in complex with either an inhibitor or with the
beta-anomer of sialic acid. The inhibitor complex reveals a typical
neuraminidase active site within a beta-propeller fold. Comparison of the
structures of the two complexes reveal differences in the active site,
suggesting that the catalytic site is activated by a conformational switch. This
site may provide both sialic acid binding and hydrolysis functions since there
is no evidence for a second sialic acid binding site in HN. Evidence for a
single site with dual functions is examined and supported by mutagenesis
studies. The structure provides the basis for the structure-based design of
inhibitors for a range of paramyxovirus-induced diseases.
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Figure 1.
Figure 1. Schematic representations of the crystal structure of
HN. The chains are colored from blue at the N-terminus
through to red at the C-terminus. The N-linked carbohydrate
residues are shown in ball and stick representation, and the
divalent metal ions are drawn as gray spheres. a, The HN dimer
observed in the orthorhombic crystal form, viewed down the NCS
two-fold axis showing the location of the  -anomer
of sialic acid drawn as a space filling molecule. b, The dimer
of the HN -Neu5Ac2en complex observed in the hexagonal crystal
form, viewed down the NCS two-fold axis. c, The image in (b)
rotated by 45° around a horizontal axis and colored according to
B-factor conveniently reveals orthogonal views of the HN
monomer. Coloring is from dark blue (B = 10 Å2) to deep red (B =
60 Å2).
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Figure 3.
Figure 3. The active site. a, The inhibitor Neu5Ac2en bound
in the active site of the hexagonal crystal form. b, The same
active site as observed in the ligand-free pH 4.6 orthorhombic
crystal structure. c, The -anomer
of sialic acid bound in the active site of the pH 4.6
orthorhombic crystal form, showing hydrogen bonding interactions
(dotted lines). Water molecules are labeled W.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2000,
7,
1068-1074)
copyright 2000.
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Secondary reference #1
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Title
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Crystallization of newcastle disease virus hemagglutinin-Neuraminidase glycoprotein.
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Authors
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T.Takimoto,
G.L.Taylor,
S.J.Crennell,
R.A.Scroggs,
A.Portner.
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Ref.
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Virology, 2000,
270,
208-214.
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PubMed id
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