Deciphering the molecular specificity of phenolic compounds as inhibitors or glycosyl acceptors of β-fructofuranosidase from Xanthophyllomyces dendrorhous

Enzymatic glycosylation of polyphenols is a tool to improve their physicochemical properties and bioavailability. On the other hand, glycosidic enzymes can be inhibited by phenolic compounds. In this work, we studied the specificity of various phenolics (hydroquinone, hydroxytyrosol, epigallocatechi...

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Autores: Ramírez-Escudero, Mercedes, Míguez Rodríguez, Noa, Gimeno Pérez, María, Ballesteros Olmo, Antonio, Fernández Lobato, María, Plou Gasca, Francisco José, Sanz‑Aparicio, Julia
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/715705
Acceso en línea:http://hdl.handle.net/10486/715705
https://dx.doi.org/10.1038/s41598-019-53948-y
Access Level:acceso abierto
Palabra clave:Phosphorylase
glucosyltransferase
sucrose
Biología y Biomedicina / Biología
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spelling Deciphering the molecular specificity of phenolic compounds as inhibitors or glycosyl acceptors of β-fructofuranosidase from Xanthophyllomyces dendrorhousRamírez-Escudero, MercedesMíguez Rodríguez, NoaGimeno Pérez, MaríaBallesteros Olmo, AntonioFernández Lobato, MaríaPlou Gasca, Francisco JoséSanz‑Aparicio, JuliaPhosphorylaseglucosyltransferasesucroseBiología y Biomedicina / BiologíaEnzymatic glycosylation of polyphenols is a tool to improve their physicochemical properties and bioavailability. On the other hand, glycosidic enzymes can be inhibited by phenolic compounds. In this work, we studied the specificity of various phenolics (hydroquinone, hydroxytyrosol, epigallocatechin gallate, catechol and p-nitrophenol) as fructosyl acceptors or inhibitors of the β-fructofuranosidase from Xanthophyllomyces dendrorhous (pXd-INV). Only hydroquinone and hydroxytyrosol gave rise to the formation of glycosylated products. For the rest, an inhibitory effect on both the hydrolytic (H) and transglycosylation (T) activity of pXd-INV, as well as an increase in the H/T ratio, was observed. To disclose the binding mode of each compound and elucidate the molecular features determining its acceptor or inhibitor behaviour, ternary complexes of the inactive mutant pXd-INV-D80A with fructose and the different polyphenols were analyzed by X-ray crystallography. All the compounds bind by stacking against Trp105 and locate one of their phenolic hydroxyls making a polar linkage to the fructose O2 at 3.6-3.8 Å from the C2, which could enable the ulterior nucleophilic attack leading to transfructosylation. Binding of hydroquinone was further investigated by soaking in absence of fructose, showing a flexible site that likely allows productive motion of the intermediates. Therefore, the acceptor capacity of the different polyphenols seems mediated by their ability to make flexible polar links with the protein, this flexibility being essential for the transfructosylation reaction to proceed. Finally, the binding affinity of the phenolic compounds was explained based on the two sites previously reported for pXd-INVTis work was supported by grants from the Spanish Ministry of Economy and Competitiveness (BIO2016- 76601-C3-1-R/2-R/3-R), the Fundación Ramón Areces (XIX Call of Research Grants in Life and Materials Sciences) and the European Union’s Horizon 2020 research and innovation program Blue Growth (Agreement No. 634486, INMARE). M.G.-P. thanks the Spanish Ministry of Education for FPU Grant. We thank the Fundación Ramón Areces by an institutional grant to the Centre of Molecular Biology Severo Ochoa (CBMSO)NLM (Medline)Departamento de Biología MolecularFacultad de Ciencias20192019-11-25research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/715705https://dx.doi.org/10.1038/s41598-019-53948-yreponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengEuropean Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 634486open accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7157052026-06-23T12:46:27Z
dc.title.none.fl_str_mv Deciphering the molecular specificity of phenolic compounds as inhibitors or glycosyl acceptors of β-fructofuranosidase from Xanthophyllomyces dendrorhous
title Deciphering the molecular specificity of phenolic compounds as inhibitors or glycosyl acceptors of β-fructofuranosidase from Xanthophyllomyces dendrorhous
spellingShingle Deciphering the molecular specificity of phenolic compounds as inhibitors or glycosyl acceptors of β-fructofuranosidase from Xanthophyllomyces dendrorhous
Ramírez-Escudero, Mercedes
Phosphorylase
glucosyltransferase
sucrose
Biología y Biomedicina / Biología
title_short Deciphering the molecular specificity of phenolic compounds as inhibitors or glycosyl acceptors of β-fructofuranosidase from Xanthophyllomyces dendrorhous
title_full Deciphering the molecular specificity of phenolic compounds as inhibitors or glycosyl acceptors of β-fructofuranosidase from Xanthophyllomyces dendrorhous
title_fullStr Deciphering the molecular specificity of phenolic compounds as inhibitors or glycosyl acceptors of β-fructofuranosidase from Xanthophyllomyces dendrorhous
title_full_unstemmed Deciphering the molecular specificity of phenolic compounds as inhibitors or glycosyl acceptors of β-fructofuranosidase from Xanthophyllomyces dendrorhous
title_sort Deciphering the molecular specificity of phenolic compounds as inhibitors or glycosyl acceptors of β-fructofuranosidase from Xanthophyllomyces dendrorhous
dc.creator.none.fl_str_mv Ramírez-Escudero, Mercedes
Míguez Rodríguez, Noa
Gimeno Pérez, María
Ballesteros Olmo, Antonio
Fernández Lobato, María
Plou Gasca, Francisco José
Sanz‑Aparicio, Julia
author Ramírez-Escudero, Mercedes
author_facet Ramírez-Escudero, Mercedes
Míguez Rodríguez, Noa
Gimeno Pérez, María
Ballesteros Olmo, Antonio
Fernández Lobato, María
Plou Gasca, Francisco José
Sanz‑Aparicio, Julia
author_role author
author2 Míguez Rodríguez, Noa
Gimeno Pérez, María
Ballesteros Olmo, Antonio
Fernández Lobato, María
Plou Gasca, Francisco José
Sanz‑Aparicio, Julia
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Biología Molecular
Facultad de Ciencias
dc.subject.none.fl_str_mv Phosphorylase
glucosyltransferase
sucrose
Biología y Biomedicina / Biología
topic Phosphorylase
glucosyltransferase
sucrose
Biología y Biomedicina / Biología
description Enzymatic glycosylation of polyphenols is a tool to improve their physicochemical properties and bioavailability. On the other hand, glycosidic enzymes can be inhibited by phenolic compounds. In this work, we studied the specificity of various phenolics (hydroquinone, hydroxytyrosol, epigallocatechin gallate, catechol and p-nitrophenol) as fructosyl acceptors or inhibitors of the β-fructofuranosidase from Xanthophyllomyces dendrorhous (pXd-INV). Only hydroquinone and hydroxytyrosol gave rise to the formation of glycosylated products. For the rest, an inhibitory effect on both the hydrolytic (H) and transglycosylation (T) activity of pXd-INV, as well as an increase in the H/T ratio, was observed. To disclose the binding mode of each compound and elucidate the molecular features determining its acceptor or inhibitor behaviour, ternary complexes of the inactive mutant pXd-INV-D80A with fructose and the different polyphenols were analyzed by X-ray crystallography. All the compounds bind by stacking against Trp105 and locate one of their phenolic hydroxyls making a polar linkage to the fructose O2 at 3.6-3.8 Å from the C2, which could enable the ulterior nucleophilic attack leading to transfructosylation. Binding of hydroquinone was further investigated by soaking in absence of fructose, showing a flexible site that likely allows productive motion of the intermediates. Therefore, the acceptor capacity of the different polyphenols seems mediated by their ability to make flexible polar links with the protein, this flexibility being essential for the transfructosylation reaction to proceed. Finally, the binding affinity of the phenolic compounds was explained based on the two sites previously reported for pXd-INV
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-11-25
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/715705
https://dx.doi.org/10.1038/s41598-019-53948-y
url http://hdl.handle.net/10486/715705
https://dx.doi.org/10.1038/s41598-019-53948-y
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv European Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 634486
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv NLM (Medline)
publisher.none.fl_str_mv NLM (Medline)
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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