Multiscale Modeling of Thiol Overoxidation in Peroxiredoxins by Hydrogen Peroxide

Autores
Semelak, Jonathan Alexis; Battistini, F.; Radi, R.; Trujillo, M.; Zeida, A.; Estrin, Dario Ariel
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In this work, we employ a multiscale quantum-classical mechanics (QM/MM) scheme to investigate the chemical reactivity of sulfenic acids toward hydrogen peroxide, both in aqueous solution and in the protein environment of the peroxiredoxin alkyl hydroperoxide reductase E from Mycobacterium tuberculosis (MtAhpE). The reaction of oxidation of cysteine with hydrogen peroxides, catalyzed by peroxiredoxins, is usually accelerated several orders of magnitude in comparison with the analogous reaction in solution. The resulting cysteine sulfenic acid is then reduced in other steps of the catalytic cycle, recovering the original thiol. However, under some conditions, the sulfenic acid can react with another equivalent of oxidant to form a sulfinic acid. This process is called overoxidation and has been associated with redox signaling. Herein, we employed a multiscale scheme based on density function theory calculations coupled to the classical AMBER force field, developed in our group, to establish the molecular basis of thiol overoxidation by hydrogen peroxide. Our results suggest that residues that play key catalytic roles in the oxidation of MtAhpE are not relevant in the overoxidation process. Indeed, the calculations propose that the process is unfavored by this particular enzyme microenvironment.
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: Battistini, F.. Barcelona Institute of Science and Technology; España
Fil: Radi, R.. Universidad de la República; Uruguay
Fil: Trujillo, M.. Universidad de la República; Uruguay
Fil: Zeida, A.. Universidad de la República; 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. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina
Materia
peroxiredoxin
QM-MM
thiol
overoxidation
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/121642
Acceder
id CONICETDig_6d2a639a19f875fc3d4314806a91bc81
oai_identifier_str oai:ri.conicet.gov.ar:11336/121642
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Multiscale Modeling of Thiol Overoxidation in Peroxiredoxins by Hydrogen PeroxideSemelak, Jonathan AlexisBattistini, F.Radi, R.Trujillo, M.Zeida, A.Estrin, Dario ArielperoxiredoxinQM-MMthioloveroxidationhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1In this work, we employ a multiscale quantum-classical mechanics (QM/MM) scheme to investigate the chemical reactivity of sulfenic acids toward hydrogen peroxide, both in aqueous solution and in the protein environment of the peroxiredoxin alkyl hydroperoxide reductase E from Mycobacterium tuberculosis (MtAhpE). The reaction of oxidation of cysteine with hydrogen peroxides, catalyzed by peroxiredoxins, is usually accelerated several orders of magnitude in comparison with the analogous reaction in solution. The resulting cysteine sulfenic acid is then reduced in other steps of the catalytic cycle, recovering the original thiol. However, under some conditions, the sulfenic acid can react with another equivalent of oxidant to form a sulfinic acid. This process is called overoxidation and has been associated with redox signaling. Herein, we employed a multiscale scheme based on density function theory calculations coupled to the classical AMBER force field, developed in our group, to establish the molecular basis of thiol overoxidation by hydrogen peroxide. Our results suggest that residues that play key catalytic roles in the oxidation of MtAhpE are not relevant in the overoxidation process. Indeed, the calculations propose that the process is unfavored by this particular enzyme microenvironment.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; ArgentinaFil: Battistini, F.. Barcelona Institute of Science and Technology; EspañaFil: Radi, R.. Universidad de la República; UruguayFil: Trujillo, M.. Universidad de la República; UruguayFil: Zeida, A.. 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; ArgentinaAmerican Chemical Society2019-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/121642Semelak, Jonathan Alexis; Battistini, F.; Radi, R.; Trujillo, M.; Zeida, A.; et al.; Multiscale Modeling of Thiol Overoxidation in Peroxiredoxins by Hydrogen Peroxide; American Chemical Society; Journal of Chemical Information and Modeling; 60; 2; 11-2019; 843-8531549-95961520-5142CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1021/acs.jcim.9b00817info:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/acs.jcim.9b00817info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:49:13Zoai:ri.conicet.gov.ar:11336/121642instacron: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 09:49:13.974CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Multiscale Modeling of Thiol Overoxidation in Peroxiredoxins by Hydrogen Peroxide
title Multiscale Modeling of Thiol Overoxidation in Peroxiredoxins by Hydrogen Peroxide
spellingShingle Multiscale Modeling of Thiol Overoxidation in Peroxiredoxins by Hydrogen Peroxide
Semelak, Jonathan Alexis
peroxiredoxin
QM-MM
thiol
overoxidation
title_short Multiscale Modeling of Thiol Overoxidation in Peroxiredoxins by Hydrogen Peroxide
title_full Multiscale Modeling of Thiol Overoxidation in Peroxiredoxins by Hydrogen Peroxide
title_fullStr Multiscale Modeling of Thiol Overoxidation in Peroxiredoxins by Hydrogen Peroxide
title_full_unstemmed Multiscale Modeling of Thiol Overoxidation in Peroxiredoxins by Hydrogen Peroxide
title_sort Multiscale Modeling of Thiol Overoxidation in Peroxiredoxins by Hydrogen Peroxide
dc.creator.none.fl_str_mv Semelak, Jonathan Alexis
Battistini, F.
Radi, R.
Trujillo, M.
Zeida, A.
Estrin, Dario Ariel
author Semelak, Jonathan Alexis
author_facet Semelak, Jonathan Alexis
Battistini, F.
Radi, R.
Trujillo, M.
Zeida, A.
Estrin, Dario Ariel
author_role author
author2 Battistini, F.
Radi, R.
Trujillo, M.
Zeida, A.
Estrin, Dario Ariel
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv peroxiredoxin
QM-MM
thiol
overoxidation
topic peroxiredoxin
QM-MM
thiol
overoxidation
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv In this work, we employ a multiscale quantum-classical mechanics (QM/MM) scheme to investigate the chemical reactivity of sulfenic acids toward hydrogen peroxide, both in aqueous solution and in the protein environment of the peroxiredoxin alkyl hydroperoxide reductase E from Mycobacterium tuberculosis (MtAhpE). The reaction of oxidation of cysteine with hydrogen peroxides, catalyzed by peroxiredoxins, is usually accelerated several orders of magnitude in comparison with the analogous reaction in solution. The resulting cysteine sulfenic acid is then reduced in other steps of the catalytic cycle, recovering the original thiol. However, under some conditions, the sulfenic acid can react with another equivalent of oxidant to form a sulfinic acid. This process is called overoxidation and has been associated with redox signaling. Herein, we employed a multiscale scheme based on density function theory calculations coupled to the classical AMBER force field, developed in our group, to establish the molecular basis of thiol overoxidation by hydrogen peroxide. Our results suggest that residues that play key catalytic roles in the oxidation of MtAhpE are not relevant in the overoxidation process. Indeed, the calculations propose that the process is unfavored by this particular enzyme microenvironment.
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: Battistini, F.. Barcelona Institute of Science and Technology; España
Fil: Radi, R.. Universidad de la República; Uruguay
Fil: Trujillo, M.. Universidad de la República; Uruguay
Fil: Zeida, A.. Universidad de la República; 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. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina
description In this work, we employ a multiscale quantum-classical mechanics (QM/MM) scheme to investigate the chemical reactivity of sulfenic acids toward hydrogen peroxide, both in aqueous solution and in the protein environment of the peroxiredoxin alkyl hydroperoxide reductase E from Mycobacterium tuberculosis (MtAhpE). The reaction of oxidation of cysteine with hydrogen peroxides, catalyzed by peroxiredoxins, is usually accelerated several orders of magnitude in comparison with the analogous reaction in solution. The resulting cysteine sulfenic acid is then reduced in other steps of the catalytic cycle, recovering the original thiol. However, under some conditions, the sulfenic acid can react with another equivalent of oxidant to form a sulfinic acid. This process is called overoxidation and has been associated with redox signaling. Herein, we employed a multiscale scheme based on density function theory calculations coupled to the classical AMBER force field, developed in our group, to establish the molecular basis of thiol overoxidation by hydrogen peroxide. Our results suggest that residues that play key catalytic roles in the oxidation of MtAhpE are not relevant in the overoxidation process. Indeed, the calculations propose that the process is unfavored by this particular enzyme microenvironment.
publishDate 2019
dc.date.none.fl_str_mv 2019-11
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/11336/121642
Semelak, Jonathan Alexis; Battistini, F.; Radi, R.; Trujillo, M.; Zeida, A.; et al.; Multiscale Modeling of Thiol Overoxidation in Peroxiredoxins by Hydrogen Peroxide; American Chemical Society; Journal of Chemical Information and Modeling; 60; 2; 11-2019; 843-853
1549-9596
1520-5142
CONICET Digital
CONICET
url http://hdl.handle.net/11336/121642
identifier_str_mv Semelak, Jonathan Alexis; Battistini, F.; Radi, R.; Trujillo, M.; Zeida, A.; et al.; Multiscale Modeling of Thiol Overoxidation in Peroxiredoxins by Hydrogen Peroxide; American Chemical Society; Journal of Chemical Information and Modeling; 60; 2; 11-2019; 843-853
1549-9596
1520-5142
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1021/acs.jcim.9b00817
info:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/acs.jcim.9b00817
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
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
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
_version_ 1844613525749628928
score 13.070432

Publicaciones similares