Molecular basis of intramolecular electron transfer in proteins during radical-mediated oxidations: Computer simulation studies in model tyrosine-cysteine peptides in solution

Experimental studies in hemeproteins and model Tyr/Cys-containing peptides exposed to oxidizing and nitrating species suggest that intramolecular electron transfer (IET) between tyrosyl radicals (Tyr-O) and Cys residues controls oxidative modification yields. The molecular basis of this IET process...

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Autores: Petruk, Ariel Alcides, Bartesaghi Hierro, Silvina María, Trujillo, Madia, Estrin, Dario Ariel, Murgida, Daniel Horacio, Kalyanaraman, Balaraman, Marti, Marcelo Adrian, Radi, Rafael
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2012
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/67726
Acceso en línea:http://hdl.handle.net/11336/67726
Access Level:acceso abierto
Palabra clave:Computer Simulation
Electron Transfer
Nitration
Oxidation
Tyrosyl Radical
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
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dc.title.none.fl_str_mv Molecular basis of intramolecular electron transfer in proteins during radical-mediated oxidations: Computer simulation studies in model tyrosine-cysteine peptides in solution
title Molecular basis of intramolecular electron transfer in proteins during radical-mediated oxidations: Computer simulation studies in model tyrosine-cysteine peptides in solution
spellingShingle Molecular basis of intramolecular electron transfer in proteins during radical-mediated oxidations: Computer simulation studies in model tyrosine-cysteine peptides in solution
Petruk, Ariel Alcides
Computer Simulation
Electron Transfer
Nitration
Oxidation
Tyrosyl Radical
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
title_short Molecular basis of intramolecular electron transfer in proteins during radical-mediated oxidations: Computer simulation studies in model tyrosine-cysteine peptides in solution
title_full Molecular basis of intramolecular electron transfer in proteins during radical-mediated oxidations: Computer simulation studies in model tyrosine-cysteine peptides in solution
title_fullStr Molecular basis of intramolecular electron transfer in proteins during radical-mediated oxidations: Computer simulation studies in model tyrosine-cysteine peptides in solution
title_full_unstemmed Molecular basis of intramolecular electron transfer in proteins during radical-mediated oxidations: Computer simulation studies in model tyrosine-cysteine peptides in solution
title_sort Molecular basis of intramolecular electron transfer in proteins during radical-mediated oxidations: Computer simulation studies in model tyrosine-cysteine peptides in solution
dc.creator.none.fl_str_mv Petruk, Ariel Alcides
Bartesaghi Hierro, Silvina María
Trujillo, Madia
Estrin, Dario Ariel
Murgida, Daniel Horacio
Kalyanaraman, Balaraman
Marti, Marcelo Adrian
Radi, Rafael
author Petruk, Ariel Alcides
author_facet Petruk, Ariel Alcides
Bartesaghi Hierro, Silvina María
Trujillo, Madia
Estrin, Dario Ariel
Murgida, Daniel Horacio
Kalyanaraman, Balaraman
Marti, Marcelo Adrian
Radi, Rafael
author_role author
author2 Bartesaghi Hierro, Silvina María
Trujillo, Madia
Estrin, Dario Ariel
Murgida, Daniel Horacio
Kalyanaraman, Balaraman
Marti, Marcelo Adrian
Radi, Rafael
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Computer Simulation
Electron Transfer
Nitration
Oxidation
Tyrosyl Radical
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
topic Computer Simulation
Electron Transfer
Nitration
Oxidation
Tyrosyl Radical
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
description Experimental studies in hemeproteins and model Tyr/Cys-containing peptides exposed to oxidizing and nitrating species suggest that intramolecular electron transfer (IET) between tyrosyl radicals (Tyr-O) and Cys residues controls oxidative modification yields. The molecular basis of this IET process is not sufficiently understood with structural atomic detail. Herein, we analyzed using molecular dynamics and quantum mechanics-based computational calculations, mechanistic possibilities for the radical transfer reaction in Tyr/Cys-containing peptides in solution and correlated them with existing experimental data. Our results support that Tyr-O to Cys radical transfer is mediated by an acid/base equilibrium that involves deprotonation of Cys to form the thiolate, followed by a likely rate-limiting transfer process to yield cysteinyl radical and a Tyr phenolate; proton uptake by Tyr completes the reaction. Both, the pKa values of the Tyr phenol and Cys thiol groups and the energetic and kinetics of the reversible IET are revealed as key physico-chemical factors. The proposed mechanism constitutes a case of sequential, acid/base equilibrium-dependent and solvent-mediated, proton-coupled electron transfer and explains the dependency of oxidative yields in Tyr/Cys peptides as a function of the number of alanine spacers. These findings contribute to explain oxidative modifications in proteins that contain sequence and/or spatially close Tyr-Cys residues. © 2012 Elsevier Inc. All rights reserved.
publishDate 2012
dc.date.none.fl_str_mv 2012-09
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/11336/67726
Petruk, Ariel Alcides; Bartesaghi Hierro, Silvina María; Trujillo, Madia; Estrin, Dario Ariel; Murgida, Daniel Horacio; et al.; Molecular basis of intramolecular electron transfer in proteins during radical-mediated oxidations: Computer simulation studies in model tyrosine-cysteine peptides in solution; Elsevier Science Inc; Archives of Biochemistry and Biophysics; 525; 1; 9-2012; 82-91
0003-9861
CONICET Digital
CONICET
url http://hdl.handle.net/11336/67726
identifier_str_mv Petruk, Ariel Alcides; Bartesaghi Hierro, Silvina María; Trujillo, Madia; Estrin, Dario Ariel; Murgida, Daniel Horacio; et al.; Molecular basis of intramolecular electron transfer in proteins during radical-mediated oxidations: Computer simulation studies in model tyrosine-cysteine peptides in solution; Elsevier Science Inc; Archives of Biochemistry and Biophysics; 525; 1; 9-2012; 82-91
0003-9861
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.abb.2012.05.012
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0003986112002123
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3414218/
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 Elsevier Science Inc
publisher.none.fl_str_mv Elsevier Science Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
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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spelling Molecular basis of intramolecular electron transfer in proteins during radical-mediated oxidations: Computer simulation studies in model tyrosine-cysteine peptides in solutionPetruk, Ariel AlcidesBartesaghi Hierro, Silvina MaríaTrujillo, MadiaEstrin, Dario ArielMurgida, Daniel HoracioKalyanaraman, BalaramanMarti, Marcelo AdrianRadi, RafaelComputer SimulationElectron TransferNitrationOxidationTyrosyl Radicalhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Experimental studies in hemeproteins and model Tyr/Cys-containing peptides exposed to oxidizing and nitrating species suggest that intramolecular electron transfer (IET) between tyrosyl radicals (Tyr-O) and Cys residues controls oxidative modification yields. The molecular basis of this IET process is not sufficiently understood with structural atomic detail. Herein, we analyzed using molecular dynamics and quantum mechanics-based computational calculations, mechanistic possibilities for the radical transfer reaction in Tyr/Cys-containing peptides in solution and correlated them with existing experimental data. Our results support that Tyr-O to Cys radical transfer is mediated by an acid/base equilibrium that involves deprotonation of Cys to form the thiolate, followed by a likely rate-limiting transfer process to yield cysteinyl radical and a Tyr phenolate; proton uptake by Tyr completes the reaction. Both, the pKa values of the Tyr phenol and Cys thiol groups and the energetic and kinetics of the reversible IET are revealed as key physico-chemical factors. The proposed mechanism constitutes a case of sequential, acid/base equilibrium-dependent and solvent-mediated, proton-coupled electron transfer and explains the dependency of oxidative yields in Tyr/Cys peptides as a function of the number of alanine spacers. These findings contribute to explain oxidative modifications in proteins that contain sequence and/or spatially close Tyr-Cys residues. © 2012 Elsevier Inc. All rights reserved.Fil: Petruk, Ariel Alcides. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Química del Noroeste. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química del Noroeste; ArgentinaFil: Bartesaghi Hierro, Silvina María. Universidad de la República; UruguayFil: Trujillo, Madia. Universidad de la República; UruguayFil: Estrin, Dario Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; ArgentinaFil: Murgida, Daniel Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; ArgentinaFil: Kalyanaraman, Balaraman. Medical College Of Wisconsin; Estados UnidosFil: Marti, Marcelo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Radi, Rafael. Universidad de la República; UruguayElsevier Science Inc2012-09info: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/11336/67726Petruk, Ariel Alcides; Bartesaghi Hierro, Silvina María; Trujillo, Madia; Estrin, Dario Ariel; Murgida, Daniel Horacio; et al.; Molecular basis of intramolecular electron transfer in proteins during radical-mediated oxidations: Computer simulation studies in model tyrosine-cysteine peptides in solution; Elsevier Science Inc; Archives of Biochemistry and Biophysics; 525; 1; 9-2012; 82-910003-9861CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.abb.2012.05.012info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0003986112002123info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3414218/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2024-05-08T14:19:30Zoai:ri.conicet.gov.ar:11336/67726instacron: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:34982024-05-08 14:19:30.587CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
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