1NNC

INFLUENZA VIRUS NEURAMINIDASE SUBTYPE N9 (TERN) COMPLEXED WITH 4-GUANIDINO-NEU5AC2EN INHIBITOR

Summary for 1NNC

• Entry DOI: 10.2210/pdb1nnc/pdb
• Descriptor: NEURAMINIDASE N9, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose, ... (7 entities in total)
• Functional Keywords: neuraminidase, sialidase, hydrolase (o-glucosyl)
• Biological source: Influenza A virus (A/tern/Australia/G70C/1975(H11N9))
• Cellular location: Virion membrane (By similarity): P03472
• Total number of polymer chains: 1
• Total formula weight: 45791.69

Authors

Varghese, J.N.,Colman, P.M. (deposition date: 1995-03-15, release date: 1996-04-03, Last modification date: 2024-10-16)

Primary citation

Varghese, J.N.,Epa, V.C.,Colman, P.M.
Three-dimensional structure of the complex of 4-guanidino-Neu5Ac2en and influenza virus neuraminidase.
Protein Sci., 4:1081-1087, 1995

PubMed Abstract: 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.

PubMed: 7549872

Experimental method

X-RAY DIFFRACTION (1.8 Å)