Structural Basis of Outstanding Multivalent Effects in Jack Bean α-Mannosidase Inhibition

Autores
Howard, Eduardo Ignacio; Cousido Siah, Alexandra; Lepage, Mathieu L.; Schneider, Jérémy P.; Bodlenner, Anne; Mitschler, André; Meli, Alessandra; Izzo, Irene; Alvarez, Hugo Ariel; Podjarny, Alberto; Compain, Philippe
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Multivalent design of glycosidase inhibitors is a promising strategy for the treatment of diseases involving enzymatic hydrolysis of glycosidic bonds in carbohydrates. An essential prerequisite for successful applications is the atomic‐level understanding of how outstanding binding enhancement occurs with multivalent inhibitors. Herein we report the first high‐resolution crystal structures of the Jack bean α‐mannosidase (JBα‐man) in apo and inhibited states. The three‐dimensional structure of JBα‐man in complex with the multimeric cyclopeptoid‐based inhibitor displaying the largest binding enhancements reported so far provides decisive insight into the molecular mechanisms underlying multivalent effects in glycosidase inhibition.
Fil: Howard, Eduardo Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; Argentina
Fil: Cousido Siah, Alexandra. Centre National de la Recherche Scientifique. Igbmc; Francia
Fil: Lepage, Mathieu L.. Université de Strasbourg; Francia
Fil: Schneider, Jérémy P.. Université de Strasbourg; Francia
Fil: Bodlenner, Anne. Université de Strasbourg; Francia
Fil: Mitschler, André. Centre National de la Recherche Scientifique. Igbmc; Francia
Fil: Meli, Alessandra. Universita di Salerno; Italia
Fil: Izzo, Irene. Universita di Salerno; Italia
Fil: Alvarez, Hugo Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; Argentina
Fil: Podjarny, Alberto. Centre National de la Recherche Scientifique. Igbmc; Francia
Fil: Compain, Philippe. Université de Strasbourg; Francia
Materia
Cyclic peptoids
Hydrolases
Iminosugars
Multivalency
X-ray diffraction
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/87935
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/87935
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Structural Basis of Outstanding Multivalent Effects in Jack Bean α-Mannosidase InhibitionHoward, Eduardo IgnacioCousido Siah, AlexandraLepage, Mathieu L.Schneider, Jérémy P.Bodlenner, AnneMitschler, AndréMeli, AlessandraIzzo, IreneAlvarez, Hugo ArielPodjarny, AlbertoCompain, PhilippeCyclic peptoidsHydrolasesIminosugarsMultivalencyX-ray diffractionhttps://purl.org/becyt/ford/1.3https://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Multivalent design of glycosidase inhibitors is a promising strategy for the treatment of diseases involving enzymatic hydrolysis of glycosidic bonds in carbohydrates. An essential prerequisite for successful applications is the atomic‐level understanding of how outstanding binding enhancement occurs with multivalent inhibitors. Herein we report the first high‐resolution crystal structures of the Jack bean α‐mannosidase (JBα‐man) in apo and inhibited states. The three‐dimensional structure of JBα‐man in complex with the multimeric cyclopeptoid‐based inhibitor displaying the largest binding enhancements reported so far provides decisive insight into the molecular mechanisms underlying multivalent effects in glycosidase inhibition.Fil: Howard, Eduardo Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; ArgentinaFil: Cousido Siah, Alexandra. Centre National de la Recherche Scientifique. Igbmc; FranciaFil: Lepage, Mathieu L.. Université de Strasbourg; FranciaFil: Schneider, Jérémy P.. Université de Strasbourg; FranciaFil: Bodlenner, Anne. Université de Strasbourg; FranciaFil: Mitschler, André. Centre National de la Recherche Scientifique. Igbmc; FranciaFil: Meli, Alessandra. Universita di Salerno; ItaliaFil: Izzo, Irene. Universita di Salerno; ItaliaFil: Alvarez, Hugo Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; ArgentinaFil: Podjarny, Alberto. Centre National de la Recherche Scientifique. Igbmc; FranciaFil: Compain, Philippe. Université de Strasbourg; FranciaWiley VCH Verlag2018-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/87935Howard, Eduardo Ignacio; Cousido Siah, Alexandra; Lepage, Mathieu L.; Schneider, Jérémy P.; Bodlenner, Anne; et al.; Structural Basis of Outstanding Multivalent Effects in Jack Bean α-Mannosidase Inhibition; Wiley VCH Verlag; Angewandte Chemie; 130; 27; 6-2018; 8134-81381433-7851CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://doi.wiley.com/10.1002/anie.201801202info:eu-repo/semantics/altIdentifier/doi/10.1002/anie.201801202info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:36:09Zoai:ri.conicet.gov.ar:11336/87935instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:36:10.05CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Structural Basis of Outstanding Multivalent Effects in Jack Bean α-Mannosidase Inhibition
title Structural Basis of Outstanding Multivalent Effects in Jack Bean α-Mannosidase Inhibition
spellingShingle Structural Basis of Outstanding Multivalent Effects in Jack Bean α-Mannosidase Inhibition
Howard, Eduardo Ignacio
Cyclic peptoids
Hydrolases
Iminosugars
Multivalency
X-ray diffraction
title_short Structural Basis of Outstanding Multivalent Effects in Jack Bean α-Mannosidase Inhibition
title_full Structural Basis of Outstanding Multivalent Effects in Jack Bean α-Mannosidase Inhibition
title_fullStr Structural Basis of Outstanding Multivalent Effects in Jack Bean α-Mannosidase Inhibition
title_full_unstemmed Structural Basis of Outstanding Multivalent Effects in Jack Bean α-Mannosidase Inhibition
title_sort Structural Basis of Outstanding Multivalent Effects in Jack Bean α-Mannosidase Inhibition
dc.creator.none.fl_str_mv Howard, Eduardo Ignacio
Cousido Siah, Alexandra
Lepage, Mathieu L.
Schneider, Jérémy P.
Bodlenner, Anne
Mitschler, André
Meli, Alessandra
Izzo, Irene
Alvarez, Hugo Ariel
Podjarny, Alberto
Compain, Philippe
author Howard, Eduardo Ignacio
author_facet Howard, Eduardo Ignacio
Cousido Siah, Alexandra
Lepage, Mathieu L.
Schneider, Jérémy P.
Bodlenner, Anne
Mitschler, André
Meli, Alessandra
Izzo, Irene
Alvarez, Hugo Ariel
Podjarny, Alberto
Compain, Philippe
author_role author
author2 Cousido Siah, Alexandra
Lepage, Mathieu L.
Schneider, Jérémy P.
Bodlenner, Anne
Mitschler, André
Meli, Alessandra
Izzo, Irene
Alvarez, Hugo Ariel
Podjarny, Alberto
Compain, Philippe
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cyclic peptoids
Hydrolases
Iminosugars
Multivalency
X-ray diffraction
topic Cyclic peptoids
Hydrolases
Iminosugars
Multivalency
X-ray diffraction
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.3
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Multivalent design of glycosidase inhibitors is a promising strategy for the treatment of diseases involving enzymatic hydrolysis of glycosidic bonds in carbohydrates. An essential prerequisite for successful applications is the atomic‐level understanding of how outstanding binding enhancement occurs with multivalent inhibitors. Herein we report the first high‐resolution crystal structures of the Jack bean α‐mannosidase (JBα‐man) in apo and inhibited states. The three‐dimensional structure of JBα‐man in complex with the multimeric cyclopeptoid‐based inhibitor displaying the largest binding enhancements reported so far provides decisive insight into the molecular mechanisms underlying multivalent effects in glycosidase inhibition.
Fil: Howard, Eduardo Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; Argentina
Fil: Cousido Siah, Alexandra. Centre National de la Recherche Scientifique. Igbmc; Francia
Fil: Lepage, Mathieu L.. Université de Strasbourg; Francia
Fil: Schneider, Jérémy P.. Université de Strasbourg; Francia
Fil: Bodlenner, Anne. Université de Strasbourg; Francia
Fil: Mitschler, André. Centre National de la Recherche Scientifique. Igbmc; Francia
Fil: Meli, Alessandra. Universita di Salerno; Italia
Fil: Izzo, Irene. Universita di Salerno; Italia
Fil: Alvarez, Hugo Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; Argentina
Fil: Podjarny, Alberto. Centre National de la Recherche Scientifique. Igbmc; Francia
Fil: Compain, Philippe. Université de Strasbourg; Francia
description Multivalent design of glycosidase inhibitors is a promising strategy for the treatment of diseases involving enzymatic hydrolysis of glycosidic bonds in carbohydrates. An essential prerequisite for successful applications is the atomic‐level understanding of how outstanding binding enhancement occurs with multivalent inhibitors. Herein we report the first high‐resolution crystal structures of the Jack bean α‐mannosidase (JBα‐man) in apo and inhibited states. The three‐dimensional structure of JBα‐man in complex with the multimeric cyclopeptoid‐based inhibitor displaying the largest binding enhancements reported so far provides decisive insight into the molecular mechanisms underlying multivalent effects in glycosidase inhibition.
publishDate 2018
dc.date.none.fl_str_mv 2018-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/87935
Howard, Eduardo Ignacio; Cousido Siah, Alexandra; Lepage, Mathieu L.; Schneider, Jérémy P.; Bodlenner, Anne; et al.; Structural Basis of Outstanding Multivalent Effects in Jack Bean α-Mannosidase Inhibition; Wiley VCH Verlag; Angewandte Chemie; 130; 27; 6-2018; 8134-8138
1433-7851
CONICET Digital
CONICET
url http://hdl.handle.net/11336/87935
identifier_str_mv Howard, Eduardo Ignacio; Cousido Siah, Alexandra; Lepage, Mathieu L.; Schneider, Jérémy P.; Bodlenner, Anne; et al.; Structural Basis of Outstanding Multivalent Effects in Jack Bean α-Mannosidase Inhibition; Wiley VCH Verlag; Angewandte Chemie; 130; 27; 6-2018; 8134-8138
1433-7851
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://doi.wiley.com/10.1002/anie.201801202
info:eu-repo/semantics/altIdentifier/doi/10.1002/anie.201801202
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley VCH Verlag
publisher.none.fl_str_mv Wiley VCH Verlag
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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