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PDBsum entry 1inx
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References listed in PDB file
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Key reference
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Title
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A sialic acid-Derived phosphonate analog inhibits different strains of influenza virus neuraminidase with different efficiencies.
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Authors
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C.L.White,
M.N.Janakiraman,
W.G.Laver,
C.Philippon,
A.Vasella,
G.M.Air,
M.Luo.
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Ref.
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J Mol Biol, 1995,
245,
623-634.
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PubMed id
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Abstract
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A phosphonate analog of N-acetyl neuraminic acid (PANA) has been designed as a
potential neuraminidase (NA) inhibitor and synthesized as both the alpha (ePANA)
and beta (aPANA) anomers. Inhibition of type A (N2) and type B NA activity by
ePANA was approximately a 100-fold better than by sialic acid, but inhibition of
type A (N9) NA was only ten-fold better than by sialic acid. The aPANA compound
was not a strong inhibitor for any of the NA strains tested. The crystal
structures at 2.4 A resolution of ePANA complexed to type A (N2) NA, type A (N9)
NA and type B NA and aPANA complexed to type A (N2) NA showed that neither of
the PANA compounds distorted the NA active site upon binding. No significant
differences in the NA-ePANA complex structures were found to explain the
anomalous inhibition of N9 neuraminidase by ePANA. We put forward the hypothesis
that an increase in the ePANA inhibition compared to that caused by sialic acid
is due to (1) a stronger electrostatic interaction between the inhibitor
phosphonyl group and the active site arginine pocket and (2) a lower distortion
energy requirement for binding of ePANA.
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Secondary reference #1
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Title
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Structure of influenza virus neuraminidase b/lee/40 complexed with sialic acid and a dehydro analog at 1.8-A resolution: implications for the catalytic mechanism.
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Authors
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M.N.Janakiraman,
C.L.White,
W.G.Laver,
G.M.Air,
M.Luo.
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Ref.
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Biochemistry, 1994,
33,
8172-8179.
[DOI no: ]
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PubMed id
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Secondary reference #2
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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 #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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Phosphonic-Acid analogs of the n-Acetyl-2-Deoxyneuraminic acids: synthesis and inhibition of vibrio choleae sialidase
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Authors
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K.Walliman,
A.Vasella.
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Ref.
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helv chim acta, 1990,
73,
1359.
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