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PDBsum entry 1f8d
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Hydrolase/hydrolase inhibitor
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PDB id
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1f8d
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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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Analysis of inhibitor binding in influenza virus neuraminidase.
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Authors
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B.J.Smith,
P.M.Colman,
M.Von itzstein,
B.Danylec,
J.N.Varghese.
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Ref.
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Protein Sci, 2001,
10,
689-696.
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PubMed id
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Abstract
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2,3-didehydro-2-deoxy-N:-acetylneuraminic acid (DANA) is a transition state
analog inhibitor of influenza virus neuraminidase (NA). Replacement of the
hydroxyl at the C9 position in DANA and 4-amino-DANA with an amine group, with
the intention of taking advantage of an increased electrostatic interaction with
a conserved acidic group in the active site to improve inhibitor binding,
significantly reduces the inhibitor activity of both compounds. The
three-dimensional X-ray structure of the complexes of these ligands and NA was
obtained to 1.4 A resolution and showed that both ligands bind isosterically to
DANA. Analysis of the geometry of the ammonium at the C4 position indicates that
Glu119 may be neutral when these ligands bind. A computational analysis of the
binding energies indicates that the substitution is successful in increasing the
energy of interaction; however, the gains that are made are not sufficient to
overcome the energy that is required to desolvate that part of the ligand that
comes in contact with the protein.
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