Show simple item record

dc.contributor.authorRyan, C
dc.contributor.authorZaitsev, V
dc.contributor.authorTindal, DJ
dc.contributor.authorDyason, JC
dc.contributor.authorThomson, RJ
dc.contributor.authorAlymova, I
dc.contributor.authorPortner, A
dc.contributor.authorvon Itzstein, M
dc.contributor.authorTaylor, G
dc.date.accessioned2017-10-30T12:30:23Z
dc.date.available2017-10-30T12:30:23Z
dc.date.issued2006
dc.date.modified2010-08-26T07:35:43Z
dc.identifier.issn0282-0080
dc.identifier.doi10.1007/s10719-006-5446-8
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.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherSpringer
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom135
dc.relation.ispartofpageto141
dc.relation.ispartofjournalGlycoconjugate Journal
dc.relation.ispartofvolume23
dc.rights.retentionY
dc.subject.fieldofresearchBiochemistry and cell biology
dc.subject.fieldofresearchMedical microbiology
dc.subject.fieldofresearchNeurosciences
dc.subject.fieldofresearchcode3101
dc.subject.fieldofresearchcode3207
dc.subject.fieldofresearchcode3209
dc.titleStructural analysis of a designed inhibitor complexed with the hemagglutinin-neuraminidase of Newcastle disease virus
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2006
gro.hasfulltextNo Full Text
gro.griffith.authorvon Itzstein, Mark
gro.griffith.authorThomson, Robin J.


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