Hypoxanthine-guanine phosphoribosyltransferase/adenylate kinase from Zobellia galactanivorans: A bifunctional catalyst for the synthesis of nucleoside-5′-mono-, di- and triphosphates

In our search for novel biocatalysts for the synthesis of nucleic acid derivatives, we found a good candidate in a putative dual-domain hypoxanthine-guanine phosphoribosyltransferase (HGPRT)/adenylate kinase (AMPK) from Zobellia galactanivorans (ZgHGPRT/AMPK). In this respect, we report for the firs...

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Autores: Acosta, Javier, Arco, Jon del, Pozo, María Luisa del, Herrera-Tapias, Beliña, Clemente-Suárez, Vicente Javier, Berenguer Carlos, José, Hidalgo Huertas, Aurelio, Fernández-Lucas, Jesús
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/708834
Acceso en línea:http://hdl.handle.net/10486/708834
https://dx.doi.org/10.3389/fbioe.2020.00677
Access Level:acceso abierto
Palabra clave:Biocatalysts
Biomolecules
Nucleic Acids
Positive Ions
Recombinant Proteins
Biología y Biomedicina / Biología
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spelling Hypoxanthine-guanine phosphoribosyltransferase/adenylate kinase from Zobellia galactanivorans: A bifunctional catalyst for the synthesis of nucleoside-5′-mono-, di- and triphosphatesAcosta, JavierArco, Jon delPozo, María Luisa delHerrera-Tapias, BeliñaClemente-Suárez, Vicente JavierBerenguer Carlos, JoséHidalgo Huertas, AurelioFernández-Lucas, JesúsBiocatalystsBiomoleculesNucleic AcidsPositive IonsRecombinant ProteinsBiología y Biomedicina / BiologíaIn our search for novel biocatalysts for the synthesis of nucleic acid derivatives, we found a good candidate in a putative dual-domain hypoxanthine-guanine phosphoribosyltransferase (HGPRT)/adenylate kinase (AMPK) from Zobellia galactanivorans (ZgHGPRT/AMPK). In this respect, we report for the first time the recombinant expression, production, and characterization of a bifunctional HGPRT/AMPK. Biochemical characterization of the recombinant protein indicates that the enzyme is a homodimer, with high activity in the pH range 6-7 and in a temperature interval from 30 to 80°C. Thermal denaturation experiments revealed that ZgHGPRT/AMPK exhibits an apparent unfolding temperature (Tm) of 45°C and a retained activity of around 80% when incubated at 40°C for 240 min. This bifunctional enzyme shows a dependence on divalent cations, with a remarkable preference for Mg2+ and Co2+ as cofactors. More interestingly, substrate specificity studies revealed ZgHGPRT/AMPK as a bifunctional enzyme, which acts as phosphoribosyltransferase or adenylate kinase depending upon the nature of the substrate. Finally, to assess the potential of ZgHGPRT/AMPK as biocatalyst for the synthesis of nucleoside-5′-mono, di- and triphosphates, the kinetic analysis of both activities (phosphoribosyltransferase and adenylate kinase) and the effect of water-miscible solvents on enzyme activity were studiedBIO2016-77031-RFrontiers MediaDepartamento de Biología MolecularFacultad de Ciencias20202020-06-24research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/708834https://dx.doi.org/10.3389/fbioe.2020.00677reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7088342026-06-23T12:46:27Z
dc.title.none.fl_str_mv Hypoxanthine-guanine phosphoribosyltransferase/adenylate kinase from Zobellia galactanivorans: A bifunctional catalyst for the synthesis of nucleoside-5′-mono-, di- and triphosphates
title Hypoxanthine-guanine phosphoribosyltransferase/adenylate kinase from Zobellia galactanivorans: A bifunctional catalyst for the synthesis of nucleoside-5′-mono-, di- and triphosphates
spellingShingle Hypoxanthine-guanine phosphoribosyltransferase/adenylate kinase from Zobellia galactanivorans: A bifunctional catalyst for the synthesis of nucleoside-5′-mono-, di- and triphosphates
Acosta, Javier
Biocatalysts
Biomolecules
Nucleic Acids
Positive Ions
Recombinant Proteins
Biología y Biomedicina / Biología
title_short Hypoxanthine-guanine phosphoribosyltransferase/adenylate kinase from Zobellia galactanivorans: A bifunctional catalyst for the synthesis of nucleoside-5′-mono-, di- and triphosphates
title_full Hypoxanthine-guanine phosphoribosyltransferase/adenylate kinase from Zobellia galactanivorans: A bifunctional catalyst for the synthesis of nucleoside-5′-mono-, di- and triphosphates
title_fullStr Hypoxanthine-guanine phosphoribosyltransferase/adenylate kinase from Zobellia galactanivorans: A bifunctional catalyst for the synthesis of nucleoside-5′-mono-, di- and triphosphates
title_full_unstemmed Hypoxanthine-guanine phosphoribosyltransferase/adenylate kinase from Zobellia galactanivorans: A bifunctional catalyst for the synthesis of nucleoside-5′-mono-, di- and triphosphates
title_sort Hypoxanthine-guanine phosphoribosyltransferase/adenylate kinase from Zobellia galactanivorans: A bifunctional catalyst for the synthesis of nucleoside-5′-mono-, di- and triphosphates
dc.creator.none.fl_str_mv Acosta, Javier
Arco, Jon del
Pozo, María Luisa del
Herrera-Tapias, Beliña
Clemente-Suárez, Vicente Javier
Berenguer Carlos, José
Hidalgo Huertas, Aurelio
Fernández-Lucas, Jesús
author Acosta, Javier
author_facet Acosta, Javier
Arco, Jon del
Pozo, María Luisa del
Herrera-Tapias, Beliña
Clemente-Suárez, Vicente Javier
Berenguer Carlos, José
Hidalgo Huertas, Aurelio
Fernández-Lucas, Jesús
author_role author
author2 Arco, Jon del
Pozo, María Luisa del
Herrera-Tapias, Beliña
Clemente-Suárez, Vicente Javier
Berenguer Carlos, José
Hidalgo Huertas, Aurelio
Fernández-Lucas, Jesús
author2_role author
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 Biocatalysts
Biomolecules
Nucleic Acids
Positive Ions
Recombinant Proteins
Biología y Biomedicina / Biología
topic Biocatalysts
Biomolecules
Nucleic Acids
Positive Ions
Recombinant Proteins
Biología y Biomedicina / Biología
description In our search for novel biocatalysts for the synthesis of nucleic acid derivatives, we found a good candidate in a putative dual-domain hypoxanthine-guanine phosphoribosyltransferase (HGPRT)/adenylate kinase (AMPK) from Zobellia galactanivorans (ZgHGPRT/AMPK). In this respect, we report for the first time the recombinant expression, production, and characterization of a bifunctional HGPRT/AMPK. Biochemical characterization of the recombinant protein indicates that the enzyme is a homodimer, with high activity in the pH range 6-7 and in a temperature interval from 30 to 80°C. Thermal denaturation experiments revealed that ZgHGPRT/AMPK exhibits an apparent unfolding temperature (Tm) of 45°C and a retained activity of around 80% when incubated at 40°C for 240 min. This bifunctional enzyme shows a dependence on divalent cations, with a remarkable preference for Mg2+ and Co2+ as cofactors. More interestingly, substrate specificity studies revealed ZgHGPRT/AMPK as a bifunctional enzyme, which acts as phosphoribosyltransferase or adenylate kinase depending upon the nature of the substrate. Finally, to assess the potential of ZgHGPRT/AMPK as biocatalyst for the synthesis of nucleoside-5′-mono, di- and triphosphates, the kinetic analysis of both activities (phosphoribosyltransferase and adenylate kinase) and the effect of water-miscible solvents on enzyme activity were studied
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-06-24
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/10486/708834
https://dx.doi.org/10.3389/fbioe.2020.00677
url http://hdl.handle.net/10486/708834
https://dx.doi.org/10.3389/fbioe.2020.00677
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
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
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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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