Show simple item record

Files in this item

Thumbnail

Item metadata

dc.contributor.authorOwen, C. David
dc.contributor.authorLukacik, Petra
dc.contributor.authorPotter, Jane A.
dc.contributor.authorSleator, Olivia
dc.contributor.authorTaylor, Garry L.
dc.contributor.authorWalsh, Martin A.
dc.date.accessioned2016-06-08T11:30:07Z
dc.date.available2016-06-08T11:30:07Z
dc.date.issued2015-11-13
dc.identifier243244258
dc.identifier0aa0a235-f600-41cf-83e9-bd721d6f2897
dc.identifier000365757500026
dc.identifier84946944104
dc.identifier000365757500026
dc.identifier.citationOwen , C D , Lukacik , P , Potter , J A , Sleator , O , Taylor , G L & Walsh , M A 2015 , ' Streptococcus pneumoniae NanC. Structural insights into the specificity and mechanism of a sialidase that produces a sialidase inhibitor ' , Journal of Biological Chemistry , vol. 290 , no. 46 , pp. 27736-27748 . https://doi.org/10.1074/jbc.M115.673632en
dc.identifier.issn0021-9258
dc.identifier.otherORCID: /0000-0001-9486-566X/work/60428031
dc.identifier.urihttps://hdl.handle.net/10023/8950
dc.descriptionThis work was supported by the Biotechnology and Biological Sciences Research Council (UK) and the Medical Research Council (UK).en
dc.description.abstractStreptococcus pneumoniae is an important human pathogen that causes a range of disease states. Sialidases are important bacterial virulence factors. There are three pneumococcal sialidases: NanA, NanB, and NanC. NanC is an unusual sialidase in that its primary reaction product is 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (Neu5Ac2en, also known as DANA), a nonspecific hydrolytic sialidase inhibitor. The production of Neu5Ac2en from α2-3-linked sialosides by the catalytic domain is confirmed within a crystal structure. A covalent complex with 3-fluoro-β-N-acetylneuraminic acid is also presented, suggesting a common mechanism with other sialidases up to the final step of product formation. A conformation change in an active site hydrophobic loop on ligand binding constricts the entrance to the active site. In addition, the distance between the catalytic acid/base (Asp-315) and the ligand anomeric carbon is unusually short. These features facilitate a novel sialidase reaction in which the final step of product formation is direct abstraction of the C3 proton by the active site aspartic acid, forming Neu5Ac2en. NanC also possesses a carbohydrate-binding module, which is shown to bind α2-3- and α2-6-linked sialosides, as well as N-acetylneuraminic acid, which is captured in the crystal structure following hydration of Neu5Ac2en by NanC. Overall, the pneumococcal sialidases show remarkable mechanistic diversity while maintaining a common structural scaffold.
dc.format.extent13
dc.format.extent3944722
dc.language.isoeng
dc.relation.ispartofJournal of Biological Chemistryen
dc.subjectGlycoside hydrolaseen
dc.subjectNeuraminidaseen
dc.subjectSialic aciden
dc.subjectSialidaseen
dc.subjectStreptococcusen
dc.subjectNanCen
dc.subjectCarbohydrate-binding moduleen
dc.subjectneu5ac2enen
dc.subjectPneumococcusen
dc.subjectQH301 Biologyen
dc.subjectQD Chemistryen
dc.subjectSDG 3 - Good Health and Well-beingen
dc.subject.lccQH301en
dc.subject.lccQDen
dc.titleStreptococcus pneumoniae NanC. Structural insights into the specificity and mechanism of a sialidase that produces a sialidase inhibitoren
dc.typeJournal articleen
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.identifier.doi10.1074/jbc.M115.673632
dc.description.statusPeer revieweden


This item appears in the following Collection(s)

Show simple item record