1F8C

Native Influenza Neuraminidase in Complex with 4-amino-2-deoxy-2,3-dehydro-N-neuraminic Acid

Summary for 1F8C

• Entry DOI: 10.2210/pdb1f8c/pdb
• Related: 7NN9
• Descriptor: NEURAMINIDASE, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: neuraminidase, hydrolase, influenza protein, glycosylated protein, 4-amino-dana, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Influenza A virus (A/tern/Australia/G70C/1975(H11N9))
• Total number of polymer chains: 1
• Total formula weight: 45974.91

Authors

Smith, B.J.,Colman, P.M.,Von Itzstein, M.,Danylec, B.,Varghese, J.N. (deposition date: 2000-06-30, release date: 2001-04-11, Last modification date: 2024-10-09)

Primary citation

Smith, B.J.,Colman, P.M.,Von Itzstein, M.,Danylec, B.,Varghese, J.N.
Analysis of inhibitor binding in influenza virus neuraminidase.
Protein Sci., 10:689-696, 2001

PubMed Abstract: 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.

PubMed: 11274459
DOI: 10.1110/ps.41801

Experimental method

X-RAY DIFFRACTION (1.7 Å)