title: Anti-viral inhibitor binding to influenza neuraminidase by MALDI mass spectrometry.
abstract: A matrix-assisted laser desorption ionization (MALDI) mass spectrometry-based approach is applied to identify active site domains within influenza neuraminidase that bind the antiviral inhibitors zanamivir (ZANA) and 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (DANA). Combined data from the tryptic and Glu-C endoproteinase digests of neuraminidase-inhibitor complexes have identified binding peptides that contain the active site residues Arg118, Glu119, Arg156, Glu276, and Tyr406. The binding of these residues was confirmed from the analysis of available X-ray crystal structures. The ability to identify peptides within the active sites of proteins and likely binding residues provides both a rapid and relatively high throughput approach with which to screen protein-drug interactions by MALDI mass spectrometry.
authors.affiliation: School of Molecular Bioscience, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Kavya
authors.initials: K
authors.lastname: Swaminathan
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Downard
mesh_terms: D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000737:chemistry*; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D009975:Orthomyxoviridae / Q000201:enzymology*; D010455:Peptides / Q000737:chemistry / Q000235:genetics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000998:Antiviral Agents; D010455:Peptides; D009439:Neuraminidase