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...

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Autores: Trastoy, Beatriz, Klontz, Erik, Orwenyo, Jared, Marina, A., Wang, Lai-Xi, Sundberg, Eric J, Guerin, Marcelo E.
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/345773
Acceso en línea:http://hdl.handle.net/10261/345773
https://api.elsevier.com/content/abstract/scopus_id/85047013840
Access Level:acceso abierto
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spelling Structural basis for the recognition of complex-type N-glycans by Endoglycosidase S.Trastoy, BeatrizKlontz, ErikOrwenyo, JaredMarina, A.Wang, Lai-XiSundberg, Eric JGuerin, Marcelo E.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.Peer reviewedSpringer NatureGuerin, Marcelo E. [0000-0001-9524-3184]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202420242018info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501http://hdl.handle.net/10261/345773https://api.elsevier.com/content/abstract/scopus_id/85047013840reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésNature CommunicationsSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3457732026-05-22T06:33:51Z
dc.title.none.fl_str_mv 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.
spellingShingle Structural basis for the recognition of complex-type N-glycans by Endoglycosidase S.
Trastoy, Beatriz
title_short 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_sort Structural basis for the recognition of complex-type N-glycans by Endoglycosidase S.
dc.creator.none.fl_str_mv Trastoy, Beatriz
Klontz, Erik
Orwenyo, Jared
Marina, A.
Wang, Lai-Xi
Sundberg, Eric J
Guerin, Marcelo E.
author Trastoy, Beatriz
author_facet Trastoy, Beatriz
Klontz, Erik
Orwenyo, Jared
Marina, A.
Wang, Lai-Xi
Sundberg, Eric J
Guerin, Marcelo E.
author_role author
author2 Klontz, Erik
Orwenyo, Jared
Marina, A.
Wang, Lai-Xi
Sundberg, Eric J
Guerin, Marcelo E.
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Guerin, Marcelo E. [0000-0001-9524-3184]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
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.
publishDate 2018
dc.date.none.fl_str_mv 2018
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/345773
https://api.elsevier.com/content/abstract/scopus_id/85047013840
url http://hdl.handle.net/10261/345773
https://api.elsevier.com/content/abstract/scopus_id/85047013840
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Nature Communications
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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