• myGriffith
    • Staff portal
    • Contact Us⌄
      • Future student enquiries 1800 677 728
      • Current student enquiries 1800 154 055
      • International enquiries +61 7 3735 6425
      • General enquiries 07 3735 7111
      • Online enquiries
      • Staff phonebook
    View Item 
    •   Home
    • Griffith Research Online
    • Journal articles
    • View Item
    • Home
    • Griffith Research Online
    • Journal articles
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

  • All of Griffith Research Online
    • Communities & Collections
    • Authors
    • By Issue Date
    • Titles
  • This Collection
    • Authors
    • By Issue Date
    • Titles
  • Statistics

  • Most Popular Items
  • Statistics by Country
  • Most Popular Authors
  • Support

  • Contact us
  • FAQs
  • Admin login

  • Login
  • The Catalytic Mechanism of Human Parainfluenza Virus Type 3 Haemagglutinin-Neuraminidase Revealed

    Author(s)
    Dirr, Larissa
    El-Deeb, Ibrahim Mustafa
    Guillon, Patrice
    Carroux, Cindy
    M. G. Chavas, Leonard
    von Itzstein, Mark
    Griffith University Author(s)
    von Itzstein, Mark
    Guillon, Patrice M.
    El-Deeb, Ibrahim Mustafa
    Carroux, Cindy
    Dirr, Larissa E.
    Year published
    2015
    Metadata
    Show full item record
    Abstract
    Human parainfluenza virus type 3 (hPIV-3) is one of the leading causes for lower respiratory tract disease in children, with neither an approved antiviral drug nor vaccine available to date. Understanding the catalytic mechanism of human parainfluenza virus haemagglutinin-neuraminidase (HN) protein is key to the design of specific inhibitors against this virus. Herein, we used 1H NMR spectroscopy, X-ray crystallography, and virological assays to study the catalytic mechanism of the HN enzyme activity and have identified the conserved Tyr530 as a key amino acid involved in catalysis. A novel 2,3-difluorosialic acid derivative ...
    View more >
    Human parainfluenza virus type 3 (hPIV-3) is one of the leading causes for lower respiratory tract disease in children, with neither an approved antiviral drug nor vaccine available to date. Understanding the catalytic mechanism of human parainfluenza virus haemagglutinin-neuraminidase (HN) protein is key to the design of specific inhibitors against this virus. Herein, we used 1H NMR spectroscopy, X-ray crystallography, and virological assays to study the catalytic mechanism of the HN enzyme activity and have identified the conserved Tyr530 as a key amino acid involved in catalysis. A novel 2,3-difluorosialic acid derivative showed prolonged enzyme inhibition and was found to react and form a covalent bond with Tyr530. Furthermore, the novel derivative exhibited enhanced potency in virus blockade assays relative to its Neu2en analogue. These outcomes open the door for a new generation of potent inhibitors against hPIV-3 HN.
    View less >
    Journal Title
    Angewandte Chemie (International Edition)
    Volume
    127
    Issue
    10
    DOI
    https://doi.org/10.1002/ange.201412243
    Subject
    Biomolecular Modelling and Design
    Structural Biology (incl. Macromolecular Modelling)
    Virology
    Chemical Sciences
    Sialidase‐Mechanismus
    Sialinsäuren
    Parainfluenzavirus
    Inhibitoren
    Hämagglutinin‐Neuraminidase
    Publication URI
    http://hdl.handle.net/10072/157482
    Collection
    • Journal articles

    Footer

    Disclaimer

    • Privacy policy
    • Copyright matters
    • CRICOS Provider - 00233E

    Tagline

    • Gold Coast
    • Logan
    • Brisbane - Queensland, Australia
    First Peoples of Australia
    • Aboriginal
    • Torres Strait Islander