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PDBsum entry 1nnc
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Hydrolase (o-glucosyl)
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PDB id
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1nnc
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References listed in PDB file
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Key reference
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Title
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Three-Dimensional structure of the complex of 4-Guanidino-Neu5ac2en and influenza virus neuraminidase.
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Authors
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J.N.Varghese,
V.C.Epa,
P.M.Colman.
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Ref.
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Protein Sci, 1995,
4,
1081-1087.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
percentage match of
88%.
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Abstract
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The three-dimensional X-ray structure of a complex of the potent neuraminidase
inhibitor 4-guanidino-Neu5Ac2en and influenza virus neuraminidase (Subtype N9)
has been obtained utilizing diffraction data to 1.8 A resolution. The
interactions of the inhibitor, solvent water molecules, and the active site
residues have been accurately determined. Six water molecules bound in the
native structure have been displaced by the inhibitor, and the active site
residues show no significant conformational changes on binding. Sialic acid, the
natural substrate, binds in a half-chair conformation that is isosteric to the
inhibitor. The conformation of the inhibitor in the active site of the X-ray
structure concurs with that obtained by theoretical calculations and validates
the structure-based design of the inhibitor. Comparison of known high-resolution
structures of neuraminidase subtypes N2, N9, and B shows good structural
conservation of the active site protein atoms, but the location of the water
molecules in the respective active sites is less conserved. In particular, the
environment of the 4-guanidino group of the inhibitor is strongly conserved and
is the basis for the antiviral action of the inhibitor across all presently
known influenza strains. Differences in the solvent structure in the active site
may be related to variation in the affinities of inhibitors to different
subtypes of neuraminidase.
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Secondary reference #1
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Title
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Rational design of potent sialidase-Based inhibitors of influenza virus replication.
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Authors
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M.Von itzstein,
W.Y.Wu,
G.B.Kok,
M.S.Pegg,
J.C.Dyason,
B.Jin,
T.Van phan,
M.L.Smythe,
H.F.White,
S.W.Oliver.
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Ref.
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Nature, 1993,
363,
418-423.
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PubMed id
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Secondary reference #2
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Title
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The structure of the complex between influenza virus neuraminidase and sialic acid, The viral receptor.
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Authors
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J.N.Varghese,
J.L.Mckimm-Breschkin,
J.B.Caldwell,
A.A.Kortt,
P.M.Colman.
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Ref.
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Proteins, 1992,
14,
327-332.
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PubMed id
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Secondary reference #3
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Title
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Refined atomic structures of n9 subtype influenza virus neuraminidase and escape mutants.
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Authors
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W.R.Tulip,
J.N.Varghese,
A.T.Baker,
A.Van donkelaar,
W.G.Laver,
R.G.Webster,
P.M.Colman.
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Ref.
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J Mol Biol, 1991,
221,
487-497.
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PubMed id
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Secondary reference #4
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Title
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Three-Dimensional structure of the neuraminidase of influenza virus a/tokyo/3/67 at 2.2 a resolution.
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Authors
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J.N.Varghese,
P.M.Colman.
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Ref.
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J Mol Biol, 1991,
221,
473-486.
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PubMed id
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Secondary reference #5
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Title
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Three-Dimensional structure of neuraminidase of subtype n9 from an avian influenza virus.
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Authors
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A.T.Baker,
J.N.Varghese,
W.G.Laver,
G.M.Air,
P.M.Colman.
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Ref.
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Proteins, 1987,
2,
111-117.
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PubMed id
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Secondary reference #6
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Title
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Structure of the influenza virus glycoprotein antigen neuraminidase at 2.9 a resolution.
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Authors
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J.N.Varghese,
W.G.Laver,
P.M.Colman.
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Ref.
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Nature, 1983,
303,
35-40.
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PubMed id
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