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Structural basis for the recognition of complex-type N-glycans by Endoglycosidase S
Endoglycosidase S (EndoS) is a bacterial endo-β-N-acetylglucosaminidase that specifically catalyzes the hydrolysis of the β-1,4 linkage between the first two N-acetylglucosamine residues of the biantennary complex-type N-linked glycans of IgG Fc regions. It is used for the chemoenzymatic synthesis o...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5951799/ https://www.ncbi.nlm.nih.gov/pubmed/29760474 http://dx.doi.org/10.1038/s41467-018-04300-x |
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author | Trastoy, Beatriz Klontz, Erik Orwenyo, Jared Marina, Alberto Wang, Lai-Xi Sundberg, Eric J. Guerin, Marcelo E. |
author_facet | Trastoy, Beatriz Klontz, Erik Orwenyo, Jared Marina, Alberto Wang, Lai-Xi Sundberg, Eric J. Guerin, Marcelo E. |
author_sort | Trastoy, Beatriz |
collection | PubMed |
description | Endoglycosidase S (EndoS) is a bacterial endo-β-N-acetylglucosaminidase that specifically catalyzes the hydrolysis of the β-1,4 linkage between the first two N-acetylglucosamine residues of the biantennary complex-type N-linked glycans of IgG Fc regions. It is used for the chemoenzymatic synthesis of homogeneously glycosylated antibodies with improved therapeutic properties, but the molecular basis for its substrate specificity is unknown. Here, we report the crystal structure of the full-length EndoS in complex with its oligosaccharide G2 product. The glycoside hydrolase domain contains two well-defined asymmetric grooves that accommodate the complex-type N-linked glycan antennae near the active site. Several loops shape the glycan binding site, thereby governing the strict substrate specificity of EndoS. Comparing the arrangement of these loops within EndoS and related endoglycosidases, reveals distinct-binding site architectures that correlate with the respective glycan specificities, providing a basis for the bioengineering of endoglycosidases to tailor the chemoenzymatic synthesis of monoclonal antibodies. |
format | Online Article Text |
id | pubmed-5951799 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-59517992018-05-16 Structural basis for the recognition of complex-type N-glycans by Endoglycosidase S Trastoy, Beatriz Klontz, Erik Orwenyo, Jared Marina, Alberto Wang, Lai-Xi Sundberg, Eric J. Guerin, Marcelo E. Nat Commun Article Endoglycosidase S (EndoS) is a bacterial endo-β-N-acetylglucosaminidase that specifically catalyzes the hydrolysis of the β-1,4 linkage between the first two N-acetylglucosamine residues of the biantennary complex-type N-linked glycans of IgG Fc regions. It is used for the chemoenzymatic synthesis of homogeneously glycosylated antibodies with improved therapeutic properties, but the molecular basis for its substrate specificity is unknown. Here, we report the crystal structure of the full-length EndoS in complex with its oligosaccharide G2 product. The glycoside hydrolase domain contains two well-defined asymmetric grooves that accommodate the complex-type N-linked glycan antennae near the active site. Several loops shape the glycan binding site, thereby governing the strict substrate specificity of EndoS. Comparing the arrangement of these loops within EndoS and related endoglycosidases, reveals distinct-binding site architectures that correlate with the respective glycan specificities, providing a basis for the bioengineering of endoglycosidases to tailor the chemoenzymatic synthesis of monoclonal antibodies. Nature Publishing Group UK 2018-05-14 /pmc/articles/PMC5951799/ /pubmed/29760474 http://dx.doi.org/10.1038/s41467-018-04300-x Text en © The Author(s) 2018 Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Trastoy, Beatriz Klontz, Erik Orwenyo, Jared Marina, Alberto Wang, Lai-Xi Sundberg, Eric J. Guerin, Marcelo E. Structural basis for the recognition of complex-type N-glycans by Endoglycosidase S |
title | Structural basis for the recognition of complex-type N-glycans by Endoglycosidase S |
title_full | Structural basis for the recognition of complex-type N-glycans by Endoglycosidase S |
title_fullStr | Structural basis for the recognition of complex-type N-glycans by Endoglycosidase S |
title_full_unstemmed | Structural basis for the recognition of complex-type N-glycans by Endoglycosidase S |
title_short | Structural basis for the recognition of complex-type N-glycans by Endoglycosidase S |
title_sort | structural basis for the recognition of complex-type n-glycans by endoglycosidase s |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5951799/ https://www.ncbi.nlm.nih.gov/pubmed/29760474 http://dx.doi.org/10.1038/s41467-018-04300-x |
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