Show simple item record

dc.contributor.authorRyan, Charlotteen_US
dc.contributor.authorZaitsev, Viateslaven_US
dc.contributor.authorTindal1159448, DavidDNUen_US
dc.contributor.authorDyason, Jeffreyen_US
dc.contributor.authorThomson, Robinen_US
dc.contributor.authorAlymova, Irinaen_US
dc.contributor.authorPorter, Allenen_US
dc.contributor.authorvon Itzstein, Marken_US
dc.contributor.authorTaylor, Garryen_US
dc.date.accessioned2017-04-24T07:56:28Z
dc.date.available2017-04-24T07:56:28Z
dc.date.issued2006en_US
dc.date.modified2010-08-26T07:35:43Z
dc.identifier.issn02820080en_US
dc.identifier.doi10.1007/s10719-006-5446-8en_AU
dc.identifier.urihttp://hdl.handle.net/10072/13715
dc.description.abstractViruses of the Paramyxoviridae family are the leading cause of respiratory disease in children. The human parainfluenza viruses (hPIV) are members of the Paramyxovirinae subfamily, which also includes mumps virus, Newcastle disease virus (NDV), Sendai virus (SV) and simian type 5 virus (SV5). On the surface of these viruses is the glycoprotein hemagglutinin-neuraminidase (HN), which is responsible for cell attachment, promotion of fusion and release of progeny virions. This multifunctional nature of HN makes it an attractive target for the development of inhibitors as a treatment for childhood respiratory diseases. Here we report the crystal structure of NDV HN in complex with a derivative of 2-deoxy-2,3-dehydro-Nacetylneuraminic acid, Neu5Ac2en, that has a functional group designed to occupy a large conserved binding pocket around the active site. The purpose of this study was to examine the effect of a bulky hydrophobic group at the O4 position of Neu5Ac2en, given the hydrophobic nature of the binding pocket. This derivative, with a benzyl group added to the O4 position of Neu5Ac2en, has an IC50 of ~10 占in a neuraminidase assay against hPIV3 HN. The IC50 value of the parent compound, Neu5Ac2en, in the same assay is ~25 卮 These results highlight the striking difference between the influenza neuraminidase and paramyxovirus HN active sites, and provide a platform for the development of improved HN inhibitors.en_US
dc.description.peerreviewedYesen_US
dc.description.publicationstatusYesen_AU
dc.languageEnglishen_US
dc.language.isoen_AU
dc.publisherSpringeren_US
dc.publisher.placeUnited Statesen_US
dc.relation.ispartofstudentpublicationNen_AU
dc.relation.ispartofpagefrom135en_US
dc.relation.ispartofpageto141en_US
dc.relation.ispartofjournalGlycoconjugate Journalen_US
dc.relation.ispartofvolume23en_US
dc.rights.retentionYen_AU
dc.subject.fieldofresearchcode270108en_US
dc.titleStructural analysis of a designed inhibitor complexed with the hemagglutinin-neuraminidase of Newcastle disease virusen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.date.issued2006
gro.hasfulltextNo Full Text


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record