Kinetic and Structural Studies of Aldehyde Oxidoreductase from Desulfovibrio gigas Reveal a Dithiolene-Based Chemistry for Enzyme Activation and Inhibition by H2O2.

Detalhes bibliográficos
Autor(a) principal: Marangon, Jacopo
Data de Publicação: 2013
Outros Autores: Correia, Hugo D., Brondino, Carlos D., Moura, José João Galhardas de, Romão, Maria João, Gonzalez, Pablo Javier, Santos-silva, Teresa Sacadura
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/21666
Resumo: This work has been supported by Fundacao para a Ciencia e a Tecnologia through the project PTDC/BIA-PRO/118377/2010 and grant number PEst-C/EQB/LA0006/2011. Funder website: www.fct.mctes.pt. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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spelling Kinetic and Structural Studies of Aldehyde Oxidoreductase from Desulfovibrio gigas Reveal a Dithiolene-Based Chemistry for Enzyme Activation and Inhibition by H2O2.RADIATION-DAMAGEDEHYDROGENASEXANTHINE-OXIDASE FAMILYTUNGSTEN ENZYMESPYRANOPTERINRADICAL FORMATIONMACROMOLECULAR CRYSTAL-STRUCTURESVALIDATIONMONONUCLEAR MOLYBDENUM ENZYMESPROTEIN CRYSTALSMACROMOLECULAR CRYSTAL-STRUCTURESMONONUCLEAR MOLYBDENUM ENZYMESXANTHINE-OXIDASE FAMILYRADIATION-DAMAGERADICAL FORMATIONPROTEIN CRYSTALSTUNGSTEN ENZYMESPYRANOPTERINDEHYDROGENASEVALIDATIONThis work has been supported by Fundacao para a Ciencia e a Tecnologia through the project PTDC/BIA-PRO/118377/2010 and grant number PEst-C/EQB/LA0006/2011. Funder website: www.fct.mctes.pt. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Mononuclear Mo-containing enzymes of the xanthine oxidase (XO) family catalyze the oxidative hydroxylation of aldehydes and heterocyclic compounds. The molybdenum active site shows a distorted square-pyramidal geometry in which two ligands, a hydroxyl/water molecule (the catalytic labile site) and a sulfido ligand, have been shown to be essential for catalysis. The XO family member aldehyde oxidoreductase from Desulfovibrio gigas (DgAOR) is an exception as presents in its catalytically competent form an equatorial oxo ligand instead of the sulfido ligand. Despite this structural difference, inactive samples of DgAOR can be activated upon incubation with dithionite plus sulfide, a procedure similar to that used for activation of desulfo-XO. The fact that DgAOR does not need a sulfido ligand for catalysis indicates that the process leading to the activation of inactive DgAOR samples is different to that of desulfo-XO. We now report a combined kinetic and X-ray crystallographic study to unveil the enzyme modification responsible for the inactivation and the chemistry that occurs at the Mo site when DgAOR is activated. In contrast to XO, which is activated by resulfuration of the Mo site, DgAOR activation/inactivation is governed by the oxidation state of the dithiolene moiety of the pyranopterin cofactor, which demonstrates the non-innocent behavior of the pyranopterin in enzyme activity. We also showed that DgAOR incubation with dithionite plus sulfide in the presence of dioxygen produces hydrogen peroxide not associated with the enzyme activation. The peroxide molecule coordinates to molybdenum in a η(2) fashion inhibiting the enzyme activity.CQFB-REQUIMTE - Centro de Química Fina e Biotecnologia (Lab. Associado REQUIMTE)DQ - Departamento de QuímicaRUNMarangon, JacopoCorreia, Hugo D.Brondino, Carlos D.Moura, José João Galhardas deRomão, Maria JoãoGonzalez, Pablo JavierSantos-silva, Teresa Sacadura2017-06-22T22:00:50Z20132013-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/21666eng1932-6203PURE: 404028https://doi.org/10.1371/journal.pone.0083234info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:08:38Zoai:run.unl.pt:10362/21666Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:26:55.494387Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Kinetic and Structural Studies of Aldehyde Oxidoreductase from Desulfovibrio gigas Reveal a Dithiolene-Based Chemistry for Enzyme Activation and Inhibition by H2O2.
title Kinetic and Structural Studies of Aldehyde Oxidoreductase from Desulfovibrio gigas Reveal a Dithiolene-Based Chemistry for Enzyme Activation and Inhibition by H2O2.
spellingShingle Kinetic and Structural Studies of Aldehyde Oxidoreductase from Desulfovibrio gigas Reveal a Dithiolene-Based Chemistry for Enzyme Activation and Inhibition by H2O2.
Marangon, Jacopo
RADIATION-DAMAGE
DEHYDROGENASE
XANTHINE-OXIDASE FAMILY
TUNGSTEN ENZYMES
PYRANOPTERIN
RADICAL FORMATION
MACROMOLECULAR CRYSTAL-STRUCTURES
VALIDATION
MONONUCLEAR MOLYBDENUM ENZYMES
PROTEIN CRYSTALS
MACROMOLECULAR CRYSTAL-STRUCTURES
MONONUCLEAR MOLYBDENUM ENZYMES
XANTHINE-OXIDASE FAMILY
RADIATION-DAMAGE
RADICAL FORMATION
PROTEIN CRYSTALS
TUNGSTEN ENZYMES
PYRANOPTERIN
DEHYDROGENASE
VALIDATION
title_short Kinetic and Structural Studies of Aldehyde Oxidoreductase from Desulfovibrio gigas Reveal a Dithiolene-Based Chemistry for Enzyme Activation and Inhibition by H2O2.
title_full Kinetic and Structural Studies of Aldehyde Oxidoreductase from Desulfovibrio gigas Reveal a Dithiolene-Based Chemistry for Enzyme Activation and Inhibition by H2O2.
title_fullStr Kinetic and Structural Studies of Aldehyde Oxidoreductase from Desulfovibrio gigas Reveal a Dithiolene-Based Chemistry for Enzyme Activation and Inhibition by H2O2.
title_full_unstemmed Kinetic and Structural Studies of Aldehyde Oxidoreductase from Desulfovibrio gigas Reveal a Dithiolene-Based Chemistry for Enzyme Activation and Inhibition by H2O2.
title_sort Kinetic and Structural Studies of Aldehyde Oxidoreductase from Desulfovibrio gigas Reveal a Dithiolene-Based Chemistry for Enzyme Activation and Inhibition by H2O2.
author Marangon, Jacopo
author_facet Marangon, Jacopo
Correia, Hugo D.
Brondino, Carlos D.
Moura, José João Galhardas de
Romão, Maria João
Gonzalez, Pablo Javier
Santos-silva, Teresa Sacadura
author_role author
author2 Correia, Hugo D.
Brondino, Carlos D.
Moura, José João Galhardas de
Romão, Maria João
Gonzalez, Pablo Javier
Santos-silva, Teresa Sacadura
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv CQFB-REQUIMTE - Centro de Química Fina e Biotecnologia (Lab. Associado REQUIMTE)
DQ - Departamento de Química
RUN
dc.contributor.author.fl_str_mv Marangon, Jacopo
Correia, Hugo D.
Brondino, Carlos D.
Moura, José João Galhardas de
Romão, Maria João
Gonzalez, Pablo Javier
Santos-silva, Teresa Sacadura
dc.subject.por.fl_str_mv RADIATION-DAMAGE
DEHYDROGENASE
XANTHINE-OXIDASE FAMILY
TUNGSTEN ENZYMES
PYRANOPTERIN
RADICAL FORMATION
MACROMOLECULAR CRYSTAL-STRUCTURES
VALIDATION
MONONUCLEAR MOLYBDENUM ENZYMES
PROTEIN CRYSTALS
MACROMOLECULAR CRYSTAL-STRUCTURES
MONONUCLEAR MOLYBDENUM ENZYMES
XANTHINE-OXIDASE FAMILY
RADIATION-DAMAGE
RADICAL FORMATION
PROTEIN CRYSTALS
TUNGSTEN ENZYMES
PYRANOPTERIN
DEHYDROGENASE
VALIDATION
topic RADIATION-DAMAGE
DEHYDROGENASE
XANTHINE-OXIDASE FAMILY
TUNGSTEN ENZYMES
PYRANOPTERIN
RADICAL FORMATION
MACROMOLECULAR CRYSTAL-STRUCTURES
VALIDATION
MONONUCLEAR MOLYBDENUM ENZYMES
PROTEIN CRYSTALS
MACROMOLECULAR CRYSTAL-STRUCTURES
MONONUCLEAR MOLYBDENUM ENZYMES
XANTHINE-OXIDASE FAMILY
RADIATION-DAMAGE
RADICAL FORMATION
PROTEIN CRYSTALS
TUNGSTEN ENZYMES
PYRANOPTERIN
DEHYDROGENASE
VALIDATION
description This work has been supported by Fundacao para a Ciencia e a Tecnologia through the project PTDC/BIA-PRO/118377/2010 and grant number PEst-C/EQB/LA0006/2011. Funder website: www.fct.mctes.pt. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
publishDate 2013
dc.date.none.fl_str_mv 2013
2013-01-01T00:00:00Z
2017-06-22T22:00:50Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/21666
url http://hdl.handle.net/10362/21666
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1932-6203
PURE: 404028
https://doi.org/10.1371/journal.pone.0083234
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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