Comparing thiol and selenol reactivity towards peroxynitrite by computer simulation

Autores
Messias Da Silva, Andresa; Rauber, Aníbal; Vuletich, Sofía; Zeida, Ari; Semelak, Jonathan Alexis; Estrin, Dario Ariel
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Peroxynitrite is a very reactive species implicated in a variety of pathophysiological cellular processes. Partic-ularly, peroxynitrite-mediated oxidation of cellular thiol-containing compounds such as cysteine residues is a keyprocess which has been extensively studied. Cysteine plays roles in many redox biochemistry pathways. Incontrast, selenocysteine, the 21st amino acid, is only present in 25 human proteins. Investigating the molecularbasis of selenocysteine’s reactivity may provide insights into its unique role in these selenocysteine-containingproteins. The two-electron oxidation of thiols or selenols by peroxynitrite is a process that is carried out bythe thiolate/selenate forms and peroxynitrous acid.In this work, we shed light on the molecular basis of the differential reactivity of both species towards per-oxynitrite by means of state-of-the-art computer simulations. We performed electronic structure calculations ofthe reaction in the methanethiolate and methaneselenolate model systems with peroxynitrous acid at differentlevels of theory using an implicit solvent scheme. In addition, we employed a multi-scale quantum mechanics/molecular mechanics approach for obtaining free energy profiles of these chemical reactions in aqueous solution,which enabled the comparison between the simulations and the available experimental data. Our results suggestthat the larger reactivity observed in the selenocysteine case at physiological pH is mainly due to the lower pKa,which affords a larger fraction of the reactive anionic species in these conditions, and in a second place to aslightly enhanced intrinsic reactivity of the selenate form due to its larger nucleophilicity.
Fil: Messias Da Silva, Andresa. 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
Fil: Rauber, Aníbal. 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
Fil: Vuletich, Sofía. 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
Fil: Zeida, Ari. Universidad de la República; Uruguay
Fil: Semelak, Jonathan Alexis. 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
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. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina
Materia
selenocysteine
peroxynitrite
QM-MM
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/265473
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/265473
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Comparing thiol and selenol reactivity towards peroxynitrite by computer simulationMessias Da Silva, AndresaRauber, AníbalVuletich, SofíaZeida, AriSemelak, Jonathan AlexisEstrin, Dario ArielselenocysteineperoxynitriteQM-MMhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Peroxynitrite is a very reactive species implicated in a variety of pathophysiological cellular processes. Partic-ularly, peroxynitrite-mediated oxidation of cellular thiol-containing compounds such as cysteine residues is a keyprocess which has been extensively studied. Cysteine plays roles in many redox biochemistry pathways. Incontrast, selenocysteine, the 21st amino acid, is only present in 25 human proteins. Investigating the molecularbasis of selenocysteine’s reactivity may provide insights into its unique role in these selenocysteine-containingproteins. The two-electron oxidation of thiols or selenols by peroxynitrite is a process that is carried out bythe thiolate/selenate forms and peroxynitrous acid.In this work, we shed light on the molecular basis of the differential reactivity of both species towards per-oxynitrite by means of state-of-the-art computer simulations. We performed electronic structure calculations ofthe reaction in the methanethiolate and methaneselenolate model systems with peroxynitrous acid at differentlevels of theory using an implicit solvent scheme. In addition, we employed a multi-scale quantum mechanics/molecular mechanics approach for obtaining free energy profiles of these chemical reactions in aqueous solution,which enabled the comparison between the simulations and the available experimental data. Our results suggestthat the larger reactivity observed in the selenocysteine case at physiological pH is mainly due to the lower pKa,which affords a larger fraction of the reactive anionic species in these conditions, and in a second place to aslightly enhanced intrinsic reactivity of the selenate form due to its larger nucleophilicity.Fil: Messias Da Silva, Andresa. 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; ArgentinaFil: Rauber, Aníbal. 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; ArgentinaFil: Vuletich, Sofía. 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; ArgentinaFil: Zeida, Ari. Universidad de la República; UruguayFil: Semelak, Jonathan Alexis. 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; ArgentinaFil: 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; ArgentinaElsevier2024-08info: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/11336/265473Messias Da Silva, Andresa; Rauber, Aníbal; Vuletich, Sofía; Zeida, Ari; Semelak, Jonathan Alexis; et al.; Comparing thiol and selenol reactivity towards peroxynitrite by computer simulation; Elsevier; Redox Biochemistry and Chemistry; 9; 8-2024; 1-82773-1766CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S2773176624000166info:eu-repo/semantics/altIdentifier/doi/10.1016/j.rbc.2024.100035info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:29:30Zoai:ri.conicet.gov.ar:11336/265473instacron: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:34982025-09-29 10:29:31.044CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Comparing thiol and selenol reactivity towards peroxynitrite by computer simulation
title Comparing thiol and selenol reactivity towards peroxynitrite by computer simulation
spellingShingle Comparing thiol and selenol reactivity towards peroxynitrite by computer simulation
Messias Da Silva, Andresa
selenocysteine
peroxynitrite
QM-MM
title_short Comparing thiol and selenol reactivity towards peroxynitrite by computer simulation
title_full Comparing thiol and selenol reactivity towards peroxynitrite by computer simulation
title_fullStr Comparing thiol and selenol reactivity towards peroxynitrite by computer simulation
title_full_unstemmed Comparing thiol and selenol reactivity towards peroxynitrite by computer simulation
title_sort Comparing thiol and selenol reactivity towards peroxynitrite by computer simulation
dc.creator.none.fl_str_mv Messias Da Silva, Andresa
Rauber, Aníbal
Vuletich, Sofía
Zeida, Ari
Semelak, Jonathan Alexis
Estrin, Dario Ariel
author Messias Da Silva, Andresa
author_facet Messias Da Silva, Andresa
Rauber, Aníbal
Vuletich, Sofía
Zeida, Ari
Semelak, Jonathan Alexis
Estrin, Dario Ariel
author_role author
author2 Rauber, Aníbal
Vuletich, Sofía
Zeida, Ari
Semelak, Jonathan Alexis
Estrin, Dario Ariel
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv selenocysteine
peroxynitrite
QM-MM
topic selenocysteine
peroxynitrite
QM-MM
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Peroxynitrite is a very reactive species implicated in a variety of pathophysiological cellular processes. Partic-ularly, peroxynitrite-mediated oxidation of cellular thiol-containing compounds such as cysteine residues is a keyprocess which has been extensively studied. Cysteine plays roles in many redox biochemistry pathways. Incontrast, selenocysteine, the 21st amino acid, is only present in 25 human proteins. Investigating the molecularbasis of selenocysteine’s reactivity may provide insights into its unique role in these selenocysteine-containingproteins. The two-electron oxidation of thiols or selenols by peroxynitrite is a process that is carried out bythe thiolate/selenate forms and peroxynitrous acid.In this work, we shed light on the molecular basis of the differential reactivity of both species towards per-oxynitrite by means of state-of-the-art computer simulations. We performed electronic structure calculations ofthe reaction in the methanethiolate and methaneselenolate model systems with peroxynitrous acid at differentlevels of theory using an implicit solvent scheme. In addition, we employed a multi-scale quantum mechanics/molecular mechanics approach for obtaining free energy profiles of these chemical reactions in aqueous solution,which enabled the comparison between the simulations and the available experimental data. Our results suggestthat the larger reactivity observed in the selenocysteine case at physiological pH is mainly due to the lower pKa,which affords a larger fraction of the reactive anionic species in these conditions, and in a second place to aslightly enhanced intrinsic reactivity of the selenate form due to its larger nucleophilicity.
Fil: Messias Da Silva, Andresa. 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
Fil: Rauber, Aníbal. 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
Fil: Vuletich, Sofía. 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
Fil: Zeida, Ari. Universidad de la República; Uruguay
Fil: Semelak, Jonathan Alexis. 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
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. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina
description Peroxynitrite is a very reactive species implicated in a variety of pathophysiological cellular processes. Partic-ularly, peroxynitrite-mediated oxidation of cellular thiol-containing compounds such as cysteine residues is a keyprocess which has been extensively studied. Cysteine plays roles in many redox biochemistry pathways. Incontrast, selenocysteine, the 21st amino acid, is only present in 25 human proteins. Investigating the molecularbasis of selenocysteine’s reactivity may provide insights into its unique role in these selenocysteine-containingproteins. The two-electron oxidation of thiols or selenols by peroxynitrite is a process that is carried out bythe thiolate/selenate forms and peroxynitrous acid.In this work, we shed light on the molecular basis of the differential reactivity of both species towards per-oxynitrite by means of state-of-the-art computer simulations. We performed electronic structure calculations ofthe reaction in the methanethiolate and methaneselenolate model systems with peroxynitrous acid at differentlevels of theory using an implicit solvent scheme. In addition, we employed a multi-scale quantum mechanics/molecular mechanics approach for obtaining free energy profiles of these chemical reactions in aqueous solution,which enabled the comparison between the simulations and the available experimental data. Our results suggestthat the larger reactivity observed in the selenocysteine case at physiological pH is mainly due to the lower pKa,which affords a larger fraction of the reactive anionic species in these conditions, and in a second place to aslightly enhanced intrinsic reactivity of the selenate form due to its larger nucleophilicity.
publishDate 2024
dc.date.none.fl_str_mv 2024-08
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/11336/265473
Messias Da Silva, Andresa; Rauber, Aníbal; Vuletich, Sofía; Zeida, Ari; Semelak, Jonathan Alexis; et al.; Comparing thiol and selenol reactivity towards peroxynitrite by computer simulation; Elsevier; Redox Biochemistry and Chemistry; 9; 8-2024; 1-8
2773-1766
CONICET Digital
CONICET
url http://hdl.handle.net/11336/265473
identifier_str_mv Messias Da Silva, Andresa; Rauber, Aníbal; Vuletich, Sofía; Zeida, Ari; Semelak, Jonathan Alexis; et al.; Comparing thiol and selenol reactivity towards peroxynitrite by computer simulation; Elsevier; Redox Biochemistry and Chemistry; 9; 8-2024; 1-8
2773-1766
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S2773176624000166
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.rbc.2024.100035
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc/2.5/ar/
dc.format.none.fl_str_mv application/pdf
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 13.070432

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