Mechanism of cysteine oxidation by peroxynitrite: an integrated experimental and theoretical study

Autores
Zeida Camacho, Ari Fernando; González Lebrero, Mariano Camilo; Radi, Rafael; Trujillo, Madia; Estrin, Dario Ariel
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Since peroxynitrite was identified as a pathophysiological agent it has been implicated in a great variety of cellular processes. Particularly, peroxynitrite mediated oxidation of cellular thiol-containing compounds such as Cys residues, is a key event which has been extensively studied. Although great advances have been accomplished, the reaction is not completely understood at the atomic level. Aiming to shed light on this subject, we present an integrated kinetic and theoretical study of the oxidation of free Cys by peroxynitrite. We determined pH-independent thermodynamic activation parameters, namely those corresponding to the reaction between the reactive species: Cys thiolate and peroxynitrous acid. We found a pH-independent activation energy of 8.2 ± 0.6 kcal/mol. Simulations were performed using state of the art hybrid quantum-classical (QM-MM) molecular dynamics simulations. Our results are consistent with a SN2 mechanism, with Cys sulfenic acid and nitrite anion as products. The activation barrier is mostly due to the alignment of sulfur's thiolate atom with the oxygen atoms of the peroxide, along with the concomitant charge reorganization and important changes in the solvation profile. This work provides an atomic detailed description of the reaction mechanism and a framework to understand the environment effects on peroxynitrite reactivity with protein thiols.
Fil: Zeida Camacho, Ari Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires; Argentina
Fil: González Lebrero, Mariano Camilo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina. Universidad de Buenos Aires; Argentina
Fil: Radi, Rafael. Universidad de la Republica; Uruguay
Fil: Trujillo, Madia. Universidad de la Republica; Uruguay
Fil: 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; Argentina. Universidad de Buenos Aires; Argentina
Materia
Thiols
Cysteine
Peroxynitrite
Oxiadtion
Redox Homeostasis
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/8107
Acceder
id CONICETDig_cd2cda310144cddf417532829412d112
oai_identifier_str oai:ri.conicet.gov.ar:11336/8107
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Mechanism of cysteine oxidation by peroxynitrite: an integrated experimental and theoretical studyZeida Camacho, Ari FernandoGonzález Lebrero, Mariano CamiloRadi, RafaelTrujillo, MadiaEstrin, Dario ArielThiolsCysteinePeroxynitriteOxiadtionRedox Homeostasishttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Since peroxynitrite was identified as a pathophysiological agent it has been implicated in a great variety of cellular processes. Particularly, peroxynitrite mediated oxidation of cellular thiol-containing compounds such as Cys residues, is a key event which has been extensively studied. Although great advances have been accomplished, the reaction is not completely understood at the atomic level. Aiming to shed light on this subject, we present an integrated kinetic and theoretical study of the oxidation of free Cys by peroxynitrite. We determined pH-independent thermodynamic activation parameters, namely those corresponding to the reaction between the reactive species: Cys thiolate and peroxynitrous acid. We found a pH-independent activation energy of 8.2 ± 0.6 kcal/mol. Simulations were performed using state of the art hybrid quantum-classical (QM-MM) molecular dynamics simulations. Our results are consistent with a SN2 mechanism, with Cys sulfenic acid and nitrite anion as products. The activation barrier is mostly due to the alignment of sulfur's thiolate atom with the oxygen atoms of the peroxide, along with the concomitant charge reorganization and important changes in the solvation profile. This work provides an atomic detailed description of the reaction mechanism and a framework to understand the environment effects on peroxynitrite reactivity with protein thiols.Fil: Zeida Camacho, Ari Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires; ArgentinaFil: González Lebrero, Mariano Camilo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina. Universidad de Buenos Aires; ArgentinaFil: Radi, Rafael. Universidad de la Republica; UruguayFil: Trujillo, Madia. Universidad de la Republica; 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; Argentina. Universidad de Buenos Aires; ArgentinaElsevier2013-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/8107Zeida Camacho, Ari Fernando; González Lebrero, Mariano Camilo; Radi, Rafael; Trujillo, Madia; Estrin, Dario Ariel; Mechanism of cysteine oxidation by peroxynitrite: an integrated experimental and theoretical study; Elsevier; Archives Of Biochemistry And Biophysics; 539; 1; 8-2013; 81-860003-9861enginfo:eu-repo/semantics/altIdentifier/url/http://dx.doi.org/10.1016/j.abb.2013.08.016info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0003986113002592info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:48:06Zoai:ri.conicet.gov.ar:11336/8107instacron: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:34982025-09-03 09:48:06.468CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Mechanism of cysteine oxidation by peroxynitrite: an integrated experimental and theoretical study
title Mechanism of cysteine oxidation by peroxynitrite: an integrated experimental and theoretical study
spellingShingle Mechanism of cysteine oxidation by peroxynitrite: an integrated experimental and theoretical study
Zeida Camacho, Ari Fernando
Thiols
Cysteine
Peroxynitrite
Oxiadtion
Redox Homeostasis
title_short Mechanism of cysteine oxidation by peroxynitrite: an integrated experimental and theoretical study
title_full Mechanism of cysteine oxidation by peroxynitrite: an integrated experimental and theoretical study
title_fullStr Mechanism of cysteine oxidation by peroxynitrite: an integrated experimental and theoretical study
title_full_unstemmed Mechanism of cysteine oxidation by peroxynitrite: an integrated experimental and theoretical study
title_sort Mechanism of cysteine oxidation by peroxynitrite: an integrated experimental and theoretical study
dc.creator.none.fl_str_mv Zeida Camacho, Ari Fernando
González Lebrero, Mariano Camilo
Radi, Rafael
Trujillo, Madia
Estrin, Dario Ariel
author Zeida Camacho, Ari Fernando
author_facet Zeida Camacho, Ari Fernando
González Lebrero, Mariano Camilo
Radi, Rafael
Trujillo, Madia
Estrin, Dario Ariel
author_role author
author2 González Lebrero, Mariano Camilo
Radi, Rafael
Trujillo, Madia
Estrin, Dario Ariel
author2_role author
author
author
author
dc.subject.none.fl_str_mv Thiols
Cysteine
Peroxynitrite
Oxiadtion
Redox Homeostasis
topic Thiols
Cysteine
Peroxynitrite
Oxiadtion
Redox Homeostasis
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
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 Since peroxynitrite was identified as a pathophysiological agent it has been implicated in a great variety of cellular processes. Particularly, peroxynitrite mediated oxidation of cellular thiol-containing compounds such as Cys residues, is a key event which has been extensively studied. Although great advances have been accomplished, the reaction is not completely understood at the atomic level. Aiming to shed light on this subject, we present an integrated kinetic and theoretical study of the oxidation of free Cys by peroxynitrite. We determined pH-independent thermodynamic activation parameters, namely those corresponding to the reaction between the reactive species: Cys thiolate and peroxynitrous acid. We found a pH-independent activation energy of 8.2 ± 0.6 kcal/mol. Simulations were performed using state of the art hybrid quantum-classical (QM-MM) molecular dynamics simulations. Our results are consistent with a SN2 mechanism, with Cys sulfenic acid and nitrite anion as products. The activation barrier is mostly due to the alignment of sulfur's thiolate atom with the oxygen atoms of the peroxide, along with the concomitant charge reorganization and important changes in the solvation profile. This work provides an atomic detailed description of the reaction mechanism and a framework to understand the environment effects on peroxynitrite reactivity with protein thiols.
Fil: Zeida Camacho, Ari Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires; Argentina
Fil: González Lebrero, Mariano Camilo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina. Universidad de Buenos Aires; Argentina
Fil: Radi, Rafael. Universidad de la Republica; Uruguay
Fil: Trujillo, Madia. Universidad de la Republica; Uruguay
Fil: 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; Argentina. Universidad de Buenos Aires; Argentina
description Since peroxynitrite was identified as a pathophysiological agent it has been implicated in a great variety of cellular processes. Particularly, peroxynitrite mediated oxidation of cellular thiol-containing compounds such as Cys residues, is a key event which has been extensively studied. Although great advances have been accomplished, the reaction is not completely understood at the atomic level. Aiming to shed light on this subject, we present an integrated kinetic and theoretical study of the oxidation of free Cys by peroxynitrite. We determined pH-independent thermodynamic activation parameters, namely those corresponding to the reaction between the reactive species: Cys thiolate and peroxynitrous acid. We found a pH-independent activation energy of 8.2 ± 0.6 kcal/mol. Simulations were performed using state of the art hybrid quantum-classical (QM-MM) molecular dynamics simulations. Our results are consistent with a SN2 mechanism, with Cys sulfenic acid and nitrite anion as products. The activation barrier is mostly due to the alignment of sulfur's thiolate atom with the oxygen atoms of the peroxide, along with the concomitant charge reorganization and important changes in the solvation profile. This work provides an atomic detailed description of the reaction mechanism and a framework to understand the environment effects on peroxynitrite reactivity with protein thiols.
publishDate 2013
dc.date.none.fl_str_mv 2013-08
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/11336/8107
Zeida Camacho, Ari Fernando; González Lebrero, Mariano Camilo; Radi, Rafael; Trujillo, Madia; Estrin, Dario Ariel; Mechanism of cysteine oxidation by peroxynitrite: an integrated experimental and theoretical study; Elsevier; Archives Of Biochemistry And Biophysics; 539; 1; 8-2013; 81-86
0003-9861
url http://hdl.handle.net/11336/8107
identifier_str_mv Zeida Camacho, Ari Fernando; González Lebrero, Mariano Camilo; Radi, Rafael; Trujillo, Madia; Estrin, Dario Ariel; Mechanism of cysteine oxidation by peroxynitrite: an integrated experimental and theoretical study; Elsevier; Archives Of Biochemistry And Biophysics; 539; 1; 8-2013; 81-86
0003-9861
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://dx.doi.org/10.1016/j.abb.2013.08.016
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0003986113002592
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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 13.13397

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