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Fucosidases from the human gut symbiont Ruminococcus gnavus
The availability and repartition of fucosylated glycans within the gastrointestinal tract contributes to the adaptation of gut bacteria species to ecological niches. To access this source of nutrients, gut bacteria encode α-l-fucosidases (fucosidases) which catalyze the hydrolysis of terminal α-l-fu...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872956/ https://www.ncbi.nlm.nih.gov/pubmed/32333083 http://dx.doi.org/10.1007/s00018-020-03514-x |
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author | Wu, Haiyang Rebello, Osmond Crost, Emmanuelle H. Owen, C. David Walpole, Samuel Bennati-Granier, Chloe Ndeh, Didier Monaco, Serena Hicks, Thomas Colvile, Anna Urbanowicz, Paulina A. Walsh, Martin A. Angulo, Jesus Spencer, Daniel I. R. Juge, Nathalie |
author_facet | Wu, Haiyang Rebello, Osmond Crost, Emmanuelle H. Owen, C. David Walpole, Samuel Bennati-Granier, Chloe Ndeh, Didier Monaco, Serena Hicks, Thomas Colvile, Anna Urbanowicz, Paulina A. Walsh, Martin A. Angulo, Jesus Spencer, Daniel I. R. Juge, Nathalie |
author_sort | Wu, Haiyang |
collection | PubMed |
description | The availability and repartition of fucosylated glycans within the gastrointestinal tract contributes to the adaptation of gut bacteria species to ecological niches. To access this source of nutrients, gut bacteria encode α-l-fucosidases (fucosidases) which catalyze the hydrolysis of terminal α-l-fucosidic linkages. We determined the substrate and linkage specificities of fucosidases from the human gut symbiont Ruminococcus gnavus. Sequence similarity network identified strain-specific fucosidases in R. gnavus ATCC 29149 and E1 strains that were further validated enzymatically against a range of defined oligosaccharides and glycoconjugates. Using a combination of glycan microarrays, mass spectrometry, isothermal titration calorimetry, crystallographic and saturation transfer difference NMR approaches, we identified a fucosidase with the capacity to recognize sialic acid-terminated fucosylated glycans (sialyl Lewis X/A epitopes) and hydrolyze α1–3/4 fucosyl linkages in these substrates without the need to remove sialic acid. Molecular dynamics simulation and docking showed that 3′-Sialyl Lewis X (sLeX) could be accommodated within the binding site of the enzyme. This specificity may contribute to the adaptation of R. gnavus strains to the infant and adult gut and has potential applications in diagnostic glycomic assays for diabetes and certain cancers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00018-020-03514-x) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-7872956 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-78729562021-02-22 Fucosidases from the human gut symbiont Ruminococcus gnavus Wu, Haiyang Rebello, Osmond Crost, Emmanuelle H. Owen, C. David Walpole, Samuel Bennati-Granier, Chloe Ndeh, Didier Monaco, Serena Hicks, Thomas Colvile, Anna Urbanowicz, Paulina A. Walsh, Martin A. Angulo, Jesus Spencer, Daniel I. R. Juge, Nathalie Cell Mol Life Sci Original Article The availability and repartition of fucosylated glycans within the gastrointestinal tract contributes to the adaptation of gut bacteria species to ecological niches. To access this source of nutrients, gut bacteria encode α-l-fucosidases (fucosidases) which catalyze the hydrolysis of terminal α-l-fucosidic linkages. We determined the substrate and linkage specificities of fucosidases from the human gut symbiont Ruminococcus gnavus. Sequence similarity network identified strain-specific fucosidases in R. gnavus ATCC 29149 and E1 strains that were further validated enzymatically against a range of defined oligosaccharides and glycoconjugates. Using a combination of glycan microarrays, mass spectrometry, isothermal titration calorimetry, crystallographic and saturation transfer difference NMR approaches, we identified a fucosidase with the capacity to recognize sialic acid-terminated fucosylated glycans (sialyl Lewis X/A epitopes) and hydrolyze α1–3/4 fucosyl linkages in these substrates without the need to remove sialic acid. Molecular dynamics simulation and docking showed that 3′-Sialyl Lewis X (sLeX) could be accommodated within the binding site of the enzyme. This specificity may contribute to the adaptation of R. gnavus strains to the infant and adult gut and has potential applications in diagnostic glycomic assays for diabetes and certain cancers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00018-020-03514-x) contains supplementary material, which is available to authorized users. Springer International Publishing 2020-04-24 2021 /pmc/articles/PMC7872956/ /pubmed/32333083 http://dx.doi.org/10.1007/s00018-020-03514-x Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Original Article Wu, Haiyang Rebello, Osmond Crost, Emmanuelle H. Owen, C. David Walpole, Samuel Bennati-Granier, Chloe Ndeh, Didier Monaco, Serena Hicks, Thomas Colvile, Anna Urbanowicz, Paulina A. Walsh, Martin A. Angulo, Jesus Spencer, Daniel I. R. Juge, Nathalie Fucosidases from the human gut symbiont Ruminococcus gnavus |
title | Fucosidases from the human gut symbiont Ruminococcus gnavus |
title_full | Fucosidases from the human gut symbiont Ruminococcus gnavus |
title_fullStr | Fucosidases from the human gut symbiont Ruminococcus gnavus |
title_full_unstemmed | Fucosidases from the human gut symbiont Ruminococcus gnavus |
title_short | Fucosidases from the human gut symbiont Ruminococcus gnavus |
title_sort | fucosidases from the human gut symbiont ruminococcus gnavus |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872956/ https://www.ncbi.nlm.nih.gov/pubmed/32333083 http://dx.doi.org/10.1007/s00018-020-03514-x |
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