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Streptococcus pneumoniae NanC. Structural insights into the specificity and mechanism of a sialidase that produces a sialidase inhibitor
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dc.contributor.author | Owen, C. David | |
dc.contributor.author | Lukacik, Petra | |
dc.contributor.author | Potter, Jane A. | |
dc.contributor.author | Sleator, Olivia | |
dc.contributor.author | Taylor, Garry L. | |
dc.contributor.author | Walsh, Martin A. | |
dc.date.accessioned | 2016-06-08T11:30:07Z | |
dc.date.available | 2016-06-08T11:30:07Z | |
dc.date.issued | 2015-11-13 | |
dc.identifier | 243244258 | |
dc.identifier | 0aa0a235-f600-41cf-83e9-bd721d6f2897 | |
dc.identifier | 000365757500026 | |
dc.identifier | 84946944104 | |
dc.identifier | 000365757500026 | |
dc.identifier.citation | Owen , 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.M115.673632 | en |
dc.identifier.issn | 0021-9258 | |
dc.identifier.other | ORCID: /0000-0001-9486-566X/work/60428031 | |
dc.identifier.uri | https://hdl.handle.net/10023/8950 | |
dc.description | This work was supported by the Biotechnology and Biological Sciences Research Council (UK) and the Medical Research Council (UK). | en |
dc.description.abstract | Streptococcus 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.extent | 13 | |
dc.format.extent | 3944722 | |
dc.language.iso | eng | |
dc.relation.ispartof | Journal of Biological Chemistry | en |
dc.subject | Glycoside hydrolase | en |
dc.subject | Neuraminidase | en |
dc.subject | Sialic acid | en |
dc.subject | Sialidase | en |
dc.subject | Streptococcus | en |
dc.subject | NanC | en |
dc.subject | Carbohydrate-binding module | en |
dc.subject | neu5ac2en | en |
dc.subject | Pneumococcus | en |
dc.subject | QH301 Biology | en |
dc.subject | QD Chemistry | en |
dc.subject | SDG 3 - Good Health and Well-being | en |
dc.subject.lcc | QH301 | en |
dc.subject.lcc | QD | en |
dc.title | Streptococcus pneumoniae NanC. Structural insights into the specificity and mechanism of a sialidase that produces a sialidase inhibitor | en |
dc.type | Journal article | en |
dc.contributor.institution | University of St Andrews. School of Biology | en |
dc.contributor.institution | University of St Andrews. Biomedical Sciences Research Complex | en |
dc.identifier.doi | 10.1074/jbc.M115.673632 | |
dc.description.status | Peer reviewed | en |
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