Human Mn-superoxide dismutase inactivation by peroxynitrite: A paradigm of metal-catalyzed tyrosine nitration: In vitro and in vivo

Autores
Demicheli, Verónica; Moreno, Diego Martin; Radi, Rafael
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Human MnSOD is a homotetramer and represents an essential mitochondrial antioxidant enzyme, which catalyzes the dismutation of superoxide radicals (O 2 - ) at near diffusion-controlled rates. Under a variety of disease conditions and in the process of aging, nitric oxide (NO) can outcompete MnSOD and react with O 2 - to yield the potent oxidant peroxynitrite (ONOO - ). Then, peroxynitrite can promote the regio-specific nitration of MnSOD at active site tyrosine 34, which turns the enzyme inactive. In this review we assess the kinetic aspects of the formation of peroxynitrite in the presence of MnSOD and the biochemical mechanisms of peroxynitrite-mediated MnSOD nitration. In particular, the central role of the Mn atom in the reaction of the enzyme with peroxynitrite (k = 1.0 × 10 5 M -1 s -1 per tetramer at pH = 7.4 and T = 37 °C) and the catalysis of nitration at the active site are disclosed. Then, we analyze at the atomic level of detail how a single oxidative post-translational modification in the enzyme, namely the nitration of tyrosine 34, results in enzyme inactivation. Herein, kinetic, molecular, structural biology and computational studies are integrated to rationalize the specificity and impact of peroxynitrite-dependent MnSOD tyrosine nitration in vitro and in vivo from both functional and structural perspectives.
Fil: Demicheli, Verónica. Universidad de la República; Uruguay
Fil: Moreno, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina
Fil: Radi, Rafael. Universidad de la Republica. Centro de Estudios Interdiciplinarios Uruguayos; Uruguay
Materia
SUPEROXIDE DISMUTASE
NITRATION
INACTIVATION
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:11336/87313
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/87313
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Human Mn-superoxide dismutase inactivation by peroxynitrite: A paradigm of metal-catalyzed tyrosine nitration: In vitro and in vivoDemicheli, VerónicaMoreno, Diego MartinRadi, RafaelSUPEROXIDE DISMUTASENITRATIONINACTIVATIONhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Human MnSOD is a homotetramer and represents an essential mitochondrial antioxidant enzyme, which catalyzes the dismutation of superoxide radicals (O 2 - ) at near diffusion-controlled rates. Under a variety of disease conditions and in the process of aging, nitric oxide (NO) can outcompete MnSOD and react with O 2 - to yield the potent oxidant peroxynitrite (ONOO - ). Then, peroxynitrite can promote the regio-specific nitration of MnSOD at active site tyrosine 34, which turns the enzyme inactive. In this review we assess the kinetic aspects of the formation of peroxynitrite in the presence of MnSOD and the biochemical mechanisms of peroxynitrite-mediated MnSOD nitration. In particular, the central role of the Mn atom in the reaction of the enzyme with peroxynitrite (k = 1.0 × 10 5 M -1 s -1 per tetramer at pH = 7.4 and T = 37 °C) and the catalysis of nitration at the active site are disclosed. Then, we analyze at the atomic level of detail how a single oxidative post-translational modification in the enzyme, namely the nitration of tyrosine 34, results in enzyme inactivation. Herein, kinetic, molecular, structural biology and computational studies are integrated to rationalize the specificity and impact of peroxynitrite-dependent MnSOD tyrosine nitration in vitro and in vivo from both functional and structural perspectives.Fil: Demicheli, Verónica. Universidad de la República; UruguayFil: Moreno, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Radi, Rafael. Universidad de la Republica. Centro de Estudios Interdiciplinarios Uruguayos; UruguayRoyal Society of Chemistry2018-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/87313Demicheli, Verónica; Moreno, Diego Martin; Radi, Rafael; Human Mn-superoxide dismutase inactivation by peroxynitrite: A paradigm of metal-catalyzed tyrosine nitration: In vitro and in vivo; Royal Society of Chemistry; Metallomics; 10; 5; 5-2018; 679-6951756-5901CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://xlink.rsc.org/?DOI=C7MT00348Jinfo:eu-repo/semantics/altIdentifier/doi/10.1039/C7MT00348Jinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:04:05Zoai:ri.conicet.gov.ar:11336/87313instacron: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:34982025-09-10 13:04:05.291CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Human Mn-superoxide dismutase inactivation by peroxynitrite: A paradigm of metal-catalyzed tyrosine nitration: In vitro and in vivo
title Human Mn-superoxide dismutase inactivation by peroxynitrite: A paradigm of metal-catalyzed tyrosine nitration: In vitro and in vivo
spellingShingle Human Mn-superoxide dismutase inactivation by peroxynitrite: A paradigm of metal-catalyzed tyrosine nitration: In vitro and in vivo
Demicheli, Verónica
SUPEROXIDE DISMUTASE
NITRATION
INACTIVATION
title_short Human Mn-superoxide dismutase inactivation by peroxynitrite: A paradigm of metal-catalyzed tyrosine nitration: In vitro and in vivo
title_full Human Mn-superoxide dismutase inactivation by peroxynitrite: A paradigm of metal-catalyzed tyrosine nitration: In vitro and in vivo
title_fullStr Human Mn-superoxide dismutase inactivation by peroxynitrite: A paradigm of metal-catalyzed tyrosine nitration: In vitro and in vivo
title_full_unstemmed Human Mn-superoxide dismutase inactivation by peroxynitrite: A paradigm of metal-catalyzed tyrosine nitration: In vitro and in vivo
title_sort Human Mn-superoxide dismutase inactivation by peroxynitrite: A paradigm of metal-catalyzed tyrosine nitration: In vitro and in vivo
dc.creator.none.fl_str_mv Demicheli, Verónica
Moreno, Diego Martin
Radi, Rafael
author Demicheli, Verónica
author_facet Demicheli, Verónica
Moreno, Diego Martin
Radi, Rafael
author_role author
author2 Moreno, Diego Martin
Radi, Rafael
author2_role author
author
dc.subject.none.fl_str_mv SUPEROXIDE DISMUTASE
NITRATION
INACTIVATION
topic SUPEROXIDE DISMUTASE
NITRATION
INACTIVATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Human MnSOD is a homotetramer and represents an essential mitochondrial antioxidant enzyme, which catalyzes the dismutation of superoxide radicals (O 2 - ) at near diffusion-controlled rates. Under a variety of disease conditions and in the process of aging, nitric oxide (NO) can outcompete MnSOD and react with O 2 - to yield the potent oxidant peroxynitrite (ONOO - ). Then, peroxynitrite can promote the regio-specific nitration of MnSOD at active site tyrosine 34, which turns the enzyme inactive. In this review we assess the kinetic aspects of the formation of peroxynitrite in the presence of MnSOD and the biochemical mechanisms of peroxynitrite-mediated MnSOD nitration. In particular, the central role of the Mn atom in the reaction of the enzyme with peroxynitrite (k = 1.0 × 10 5 M -1 s -1 per tetramer at pH = 7.4 and T = 37 °C) and the catalysis of nitration at the active site are disclosed. Then, we analyze at the atomic level of detail how a single oxidative post-translational modification in the enzyme, namely the nitration of tyrosine 34, results in enzyme inactivation. Herein, kinetic, molecular, structural biology and computational studies are integrated to rationalize the specificity and impact of peroxynitrite-dependent MnSOD tyrosine nitration in vitro and in vivo from both functional and structural perspectives.
Fil: Demicheli, Verónica. Universidad de la República; Uruguay
Fil: Moreno, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina
Fil: Radi, Rafael. Universidad de la Republica. Centro de Estudios Interdiciplinarios Uruguayos; Uruguay
description Human MnSOD is a homotetramer and represents an essential mitochondrial antioxidant enzyme, which catalyzes the dismutation of superoxide radicals (O 2 - ) at near diffusion-controlled rates. Under a variety of disease conditions and in the process of aging, nitric oxide (NO) can outcompete MnSOD and react with O 2 - to yield the potent oxidant peroxynitrite (ONOO - ). Then, peroxynitrite can promote the regio-specific nitration of MnSOD at active site tyrosine 34, which turns the enzyme inactive. In this review we assess the kinetic aspects of the formation of peroxynitrite in the presence of MnSOD and the biochemical mechanisms of peroxynitrite-mediated MnSOD nitration. In particular, the central role of the Mn atom in the reaction of the enzyme with peroxynitrite (k = 1.0 × 10 5 M -1 s -1 per tetramer at pH = 7.4 and T = 37 °C) and the catalysis of nitration at the active site are disclosed. Then, we analyze at the atomic level of detail how a single oxidative post-translational modification in the enzyme, namely the nitration of tyrosine 34, results in enzyme inactivation. Herein, kinetic, molecular, structural biology and computational studies are integrated to rationalize the specificity and impact of peroxynitrite-dependent MnSOD tyrosine nitration in vitro and in vivo from both functional and structural perspectives.
publishDate 2018
dc.date.none.fl_str_mv 2018-05
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/11336/87313
Demicheli, Verónica; Moreno, Diego Martin; Radi, Rafael; Human Mn-superoxide dismutase inactivation by peroxynitrite: A paradigm of metal-catalyzed tyrosine nitration: In vitro and in vivo; Royal Society of Chemistry; Metallomics; 10; 5; 5-2018; 679-695
1756-5901
CONICET Digital
CONICET
url http://hdl.handle.net/11336/87313
identifier_str_mv Demicheli, Verónica; Moreno, Diego Martin; Radi, Rafael; Human Mn-superoxide dismutase inactivation by peroxynitrite: A paradigm of metal-catalyzed tyrosine nitration: In vitro and in vivo; Royal Society of Chemistry; Metallomics; 10; 5; 5-2018; 679-695
1756-5901
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://xlink.rsc.org/?DOI=C7MT00348J
info:eu-repo/semantics/altIdentifier/doi/10.1039/C7MT00348J
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 Royal Society of Chemistry
publisher.none.fl_str_mv Royal Society of Chemistry
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 12.993085

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