dc.creator | Bell, Andrew | es |
dc.creator | Severi, Emmanuele | es |
dc.creator | Lee, Micah | es |
dc.creator | Monaco, Serena | es |
dc.creator | Latousakis, Dimitrios | es |
dc.creator | Angulo, Jesús | es |
dc.creator | Thomas, Gavin H. | es |
dc.creator | Naismith, James H. | es |
dc.creator | Juge, Nathalie | es |
dc.date.accessioned | 2020-12-14T13:08:08Z | |
dc.date.available | 2020-12-14T13:08:08Z | |
dc.date.issued | 2020 | |
dc.identifier.citation | Bell, A., Severi, ., Lee, M., Monaco, S., Latousakis, D., Angulo, J.,...,Juge, N. (2020). Uncovering a novel molecular mechanism for scavenging sialic acids in bacteria. Journal of Biological Chemistry, 295 (40), 13724-13736. | |
dc.identifier.issn | 1083-351X | es |
dc.identifier.uri | https://hdl.handle.net/11441/103186 | |
dc.description.abstract | The human gut symbiont Ruminococcus gnavus scavenges host-derived N-acetylneuraminic acid (Neu5Ac) from mucins by converting it to 2,7-anhydro-Neu5Ac. We previously showed that 2,7-anhydro-Neu5Ac is transported into R. gnavus ATCC 29149 before being converted back to Neu5Ac for further metabolic processing. However, the molecular mechanism leading to the conversion of 2,7-anhydro-Neu5Ac to Neu5Ac remained elusive. Using 1D and 2D NMR, we elucidated the multistep enzymatic mechanism of the oxidoreductase (RgNanOx) that leads to the reversible conversion of 2,7-anhydro-Neu5Ac to Neu5Ac through formation of a 4-keto-2-deoxy-2,3-dehydro-N-acetylneuraminic acid intermediate and NAD+ regeneration. The crystal structure of RgNanOx in complex with the NAD+ cofactor showed a protein dimer with a Rossman fold. Guided by the RgNanOx structure, we identified catalytic residues by site-directed mutagenesis. Bioinformatics analyses revealed the presence of RgNanOx homologues across Gram-negative and Gram-positive bacterial species and co-occurrence with sialic acid transporters. We showed by electrospray ionization spray MS that the Escherichia coli homologue YjhC displayed activity against 2,7-anhydro-Neu5Ac and that E. coli could catabolize 2,7-anhydro-Neu5Ac. Differential scanning fluorimetry analyses confirmed the binding of YjhC to the substrates 2,7-anhydro-Neu5Ac and Neu5Ac, as well as to co-factors NAD and NADH. Finally, using E. coli mutants and complementation growth assays, we demonstrated that 2,7-anhydro-Neu5Ac catabolism in E. coli depended on YjhC and on the predicted sialic acid transporter YjhB. These results revealed the molecular mechanisms of 2,7-anhydro-Neu5Ac catabolism across bacterial species and a novel sialic acid transport and catabolism pathway in E. coli. | es |
dc.format | application/pdf | es |
dc.format.extent | 12 p. | es |
dc.language.iso | eng | es |
dc.publisher | American Society for Biochemistry and Molecular Biology | es |
dc.relation.ispartof | Journal of Biological Chemistry, 295 (40), 13724-13736. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | sialic acid | es |
dc.subject | 2,7-anhydro-Neu5Ac | es |
dc.subject | gut microbiota | es |
dc.subject | mucin glycosylation | es |
dc.subject | Ruminococcus gnavus | es |
dc.subject | Escherichia coli | es |
dc.subject | sialic acid transporters | es |
dc.subject | symbiosis | es |
dc.subject | sialic acid | es |
dc.subject | microbiology | es |
dc.subject | nuclear magnetic resonance (NMR) | es |
dc.subject | Escherichia coli (E. coli) | es |
dc.subject | oxidation-reduction (redox) | es |
dc.subject | 2,7-anhydro-Neu5AC | es |
dc.subject | gut symbiosis | es |
dc.title | Uncovering a novel molecular mechanism for scavenging sialic acids in bacteria | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Química orgánica | es |
dc.relation.publisherversion | http://dx.doi.org/10.1074/jbc.RA120.014454 | es |
dc.identifier.doi | 10.1074/jbc.RA120.014454 | es |
dc.journaltitle | Journal of Biological Chemistry | es |
dc.publication.volumen | 295 | es |
dc.publication.issue | 40 | es |
dc.publication.initialPage | 13724 | es |
dc.publication.endPage | 13736 | es |