Analysis of inhibitor binding in influenza virus neuraminidase

Citation
Bj. Smith et al., Analysis of inhibitor binding in influenza virus neuraminidase, PROTEIN SCI, 10(4), 2001, pp. 689-696
Citations number
52
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
PROTEIN SCIENCE
ISSN journal
0961-8368 → ACNP
Volume
10
Issue
4
Year of publication
2001
Pages
689 - 696
Database
ISI
SICI code
0961-8368(200104)10:4<689:AOIBII>2.0.ZU;2-4
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 C-9 position in DANA and 4-amino-DANA with an amine group, with the intention of taking advantage of an increased electrostatic intera ction with a conserved acidic group in the active site to improve inhibitor binding, significantly reduces the inhibitor activity of both compounds. T he three-dimensional X-ray structure of the complexes of these ligands and NA was obtained to 1.4 Angstrom resolution and showed that both ligands bin d isosterically to DANA. Analysis of the geometry of the ammonium at the C- 4 position indicates that Glu119 may be neutral when these ligands bind. A computational analysis of the binding energies indicates that the substitut ion is successful in increasing the energy of interaction; however, the gai ns 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 protei n.