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dc.contributor.authorMoustafa, Ibrahimen_US
dc.contributor.authorConnaris, Helenen_US
dc.contributor.authorTaylor, Margareten_US
dc.contributor.authorZaitsev, Viateslaven_US
dc.contributor.authorWilson, Jennyen_US
dc.contributor.authorKiefel, Miltonen_US
dc.contributor.authorvon Itzstein, Marken_US
dc.contributor.authorTaylor, Garryen_US
dc.contributor.editorHerbert Taboren_US
dc.date.accessioned2017-05-03T11:05:38Z
dc.date.available2017-05-03T11:05:38Z
dc.date.issued2004en_US
dc.date.modified2012-02-10T02:00:56Z
dc.identifier.issn00219258en_US
dc.identifier.doi10.1074/jbc.M404965200en_US
dc.identifier.urihttp://hdl.handle.net/10072/5050
dc.description.abstractVibrio cholerae neuraminidase (VCNA) plays a significant role in the pathogenesis of cholera by removing sialic acid from higher order gangliosides to unmask GM1, the receptor for cholera toxin. We previously showed that the structure of VCNA is composed of a central ?-propeller catalytic domain flanked by two lectin-like domains, however the nature of the carbohydrates recognised by these lectin domains has remained unknown. We present here structures of the enzyme in complex with two substrates, ?2,3-sialyllactose and ?-2,6-sialyllactose. Both substrate complexes reveal the ?-anomer of N-acetylneuraminic acid (Neu5Ac, NANA) bound to the Nterminal lectin domain, thereby revealing the role of this domain. The large number of interactions suggest a relatively high binding affinity for sialic acid, which was confirmed by calorimetry, which gave a Kd~30?M. Saturation transfer difference (STD) NMR using a non-hydrolysable substrate, Neu5,9Ac2-2-S-(?-2,6)-GlcNAc?1Me, was also used to map the ligand interactions at the VCNA lectin binding site. It is well known that VCNA can hydrolyse both ?-2,3- and ?-2,6-linked sialic acid substrates. In this study using ?-2,3-sialyllactose co-crystallised with VCNA it was revealed that the inhibitor 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (Neu5Ac2en, DANA) was bound at the catalytic site. This observation supports the notion that VCNA can produce its own inhibitor and has been further confirmed by 1H NMR analysis. The discovery of the sialic acid-binding site in the N-lectin-like domain suggests that this might help target VCNA to sialic acid-rich environments, thereby enhancing the catalytic efficiency of the enzyme.en_US
dc.description.peerreviewedYesen_US
dc.description.publicationstatusYesen_US
dc.languageEnglishen_US
dc.language.isoen_US
dc.publisherAmerican Society for Biochemistry and molecular Biology Incen_US
dc.publisher.placeUSAen_US
dc.publisher.urihttp://www.jbc.org/en_US
dc.relation.ispartofpagefrom40819en_US
dc.relation.ispartofpageto40826en_US
dc.relation.ispartofissue39en_US
dc.relation.ispartofjournalJournal of Biological Chemistryen_US
dc.relation.ispartofvolume279en_US
dc.subject.fieldofresearchHISTORY AND ARCHAEOLOGYen_US
dc.subject.fieldofresearchcode210000en_US
dc.titleSialic acid recognition by Vibrio cholerae neuraminidaseen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.rights.copyrightCopyright 2004 American Society for Biochemistry and Molecular Biology. Please refer to the journal website for access to the definitive, published version.en_US
gro.date.issued2004
gro.hasfulltextNo Full Text


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