1f8b
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NATIVE INFLUENZA VIRUS NEURAMINIDASE IN COMPLEX WITH NEU5AC2EN
OverviewOverview
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.
About this StructureAbout this Structure
1F8B is a Single protein structure of sequence from Influenza a virus with NAG, CA and DAN as ligands. Active as Exo-alpha-sialidase, with EC number 3.2.1.18 Full crystallographic information is available from OCA.
ReferenceReference
Analysis of inhibitor binding in influenza virus neuraminidase., Smith BJ, Colman PM, Von Itzstein M, Danylec B, Varghese JN, Protein Sci. 2001 Apr;10(4):689-96. PMID:11274459
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