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dc.contributor.author
Demicheli, Verónica
dc.contributor.author
Moreno, Diego Martin
dc.contributor.author
Radi, Rafael
dc.date.available
2019-10-25T20:44:30Z
dc.date.issued
2018-05
dc.identifier.citation
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
dc.identifier.issn
1756-5901
dc.identifier.uri
http://hdl.handle.net/11336/87313
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Royal Society of Chemistry
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
SUPEROXIDE DISMUTASE
dc.subject
NITRATION
dc.subject
INACTIVATION
dc.subject.classification
Otras Ciencias Químicas
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Ciencias Químicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Human Mn-superoxide dismutase inactivation by peroxynitrite: A paradigm of metal-catalyzed tyrosine nitration: In vitro and in vivo
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-10-16T19:29:46Z
dc.journal.volume
10
dc.journal.number
5
dc.journal.pagination
679-695
dc.journal.pais
Reino Unido
dc.description.fil
Fil: Demicheli, Verónica. Universidad de la República; Uruguay
dc.description.fil
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
dc.description.fil
Fil: Radi, Rafael. Universidad de la Republica. Centro de Estudios Interdiciplinarios Uruguayos; Uruguay
dc.journal.title
Metallomics
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://xlink.rsc.org/?DOI=C7MT00348J
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1039/C7MT00348J
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