Unraveling the effects of peroxiredoxin 2 nitration; role of C-terminal tyrosine 193

Autores
Randall, Lía M.; Dalla Rizza, Joaquín; Parsonage, Derek; Santos, Javier; Mehl, Ryan A.; Lowther, W. Todd; Poole, Leslie B.; Denicola, Ana
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Peroxiredoxins (Prx) are enzymes that efficiently reduce hydroperoxides through active participation of cysteine residues (CP, CR). The first step in catalysis, the reduction of peroxide substrate, is fast, 107 - 108 M−1s−1 for human Prx2. In addition, the high intracellular concentration of Prx positions them not only as good antioxidants but also as central players in redox signaling pathways. These biological functions can be affected by post-translational modifications that could alter the peroxidase activity and/or interaction with other proteins. In particular, inactivation by hyperoxidation of CP, which occurs when a second molecule of peroxide reacts with the CP in the sulfenic acid form, modulates their participation in redox signaling pathways. The higher sensitivity to hyperoxidation of some Prx has been related to the presence of structural motifs that disfavor disulfide formation at the active site, making the CP sulfenic acid more available for hyperoxidation or interaction with a redox protein target. We previously reported that treatment of human Prx2 with peroxynitrite results in tyrosine nitration, a post-translational modification on non-catalytic residues, yielding a more active peroxidase with higher resistance to hyperoxidation. In this work, studies on various mutants of hPrx2 confirm that the presence of the tyrosyl side-chain of Y193, belonging to the C-terminal YF motif of eukaryotic Prx, is necessary to observe the increase in Prx2 resistance to hyperoxidation. Moreover, our results underline the critical role of this structural motif on the rate of disulfide formation that determines the differential participation of Prx in redox signaling pathways.
Fil: Randall, Lía M.. Universidad de la República; Uruguay
Fil: Dalla Rizza, Joaquín. Universidad de la Republica; Uruguay
Fil: Parsonage, Derek. Wake Forest School of Medicine; Estados Unidos
Fil: Santos, Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Mehl, Ryan A.. University of Oregon; Estados Unidos
Fil: Lowther, W. Todd. Wake Forest School of Medicine; Estados Unidos
Fil: Poole, Leslie B.. Wake Forest School of Medicine; Estados Unidos
Fil: Denicola, Ana. Universidad de la República; Uruguay
Materia
HYDROGEN PEROXIDE
HYPEROXIDATION
OXIDATIVE STRESS
PEROXIREDOXIN
PEROXYNITRITE
POST‐TRANSLATIONAL MODIFICATION (PTM)
REDOX SIGNALING
TYROSINE NITRATION
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:11336/162440
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/162440
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Unraveling the effects of peroxiredoxin 2 nitration; role of C-terminal tyrosine 193Randall, Lía M.Dalla Rizza, JoaquínParsonage, DerekSantos, JavierMehl, Ryan A.Lowther, W. ToddPoole, Leslie B.Denicola, AnaHYDROGEN PEROXIDEHYPEROXIDATIONOXIDATIVE STRESSPEROXIREDOXINPEROXYNITRITEPOST‐TRANSLATIONAL MODIFICATION (PTM)REDOX SIGNALINGTYROSINE NITRATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Peroxiredoxins (Prx) are enzymes that efficiently reduce hydroperoxides through active participation of cysteine residues (CP, CR). The first step in catalysis, the reduction of peroxide substrate, is fast, 107 - 108 M−1s−1 for human Prx2. In addition, the high intracellular concentration of Prx positions them not only as good antioxidants but also as central players in redox signaling pathways. These biological functions can be affected by post-translational modifications that could alter the peroxidase activity and/or interaction with other proteins. In particular, inactivation by hyperoxidation of CP, which occurs when a second molecule of peroxide reacts with the CP in the sulfenic acid form, modulates their participation in redox signaling pathways. The higher sensitivity to hyperoxidation of some Prx has been related to the presence of structural motifs that disfavor disulfide formation at the active site, making the CP sulfenic acid more available for hyperoxidation or interaction with a redox protein target. We previously reported that treatment of human Prx2 with peroxynitrite results in tyrosine nitration, a post-translational modification on non-catalytic residues, yielding a more active peroxidase with higher resistance to hyperoxidation. In this work, studies on various mutants of hPrx2 confirm that the presence of the tyrosyl side-chain of Y193, belonging to the C-terminal YF motif of eukaryotic Prx, is necessary to observe the increase in Prx2 resistance to hyperoxidation. Moreover, our results underline the critical role of this structural motif on the rate of disulfide formation that determines the differential participation of Prx in redox signaling pathways.Fil: Randall, Lía M.. Universidad de la República; UruguayFil: Dalla Rizza, Joaquín. Universidad de la Republica; UruguayFil: Parsonage, Derek. Wake Forest School of Medicine; Estados UnidosFil: Santos, Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Mehl, Ryan A.. University of Oregon; Estados UnidosFil: Lowther, W. Todd. Wake Forest School of Medicine; Estados UnidosFil: Poole, Leslie B.. Wake Forest School of Medicine; Estados UnidosFil: Denicola, Ana. Universidad de la República; UruguayElsevier Science Inc.2019-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/162440Randall, Lía M.; Dalla Rizza, Joaquín; Parsonage, Derek; Santos, Javier; Mehl, Ryan A.; et al.; Unraveling the effects of peroxiredoxin 2 nitration; role of C-terminal tyrosine 193; Elsevier Science Inc.; Free Radical Biology and Medicine; 141; 9-2019; 492-5010891-5849CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0891584919304629info:eu-repo/semantics/altIdentifier/doi/10.1016/j.freeradbiomed.2019.07.016info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:06:42Zoai:ri.conicet.gov.ar:11336/162440instacron: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:34982025-10-15 15:06:43.278CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Unraveling the effects of peroxiredoxin 2 nitration; role of C-terminal tyrosine 193
title Unraveling the effects of peroxiredoxin 2 nitration; role of C-terminal tyrosine 193
spellingShingle Unraveling the effects of peroxiredoxin 2 nitration; role of C-terminal tyrosine 193
Randall, Lía M.
HYDROGEN PEROXIDE
HYPEROXIDATION
OXIDATIVE STRESS
PEROXIREDOXIN
PEROXYNITRITE
POST‐TRANSLATIONAL MODIFICATION (PTM)
REDOX SIGNALING
TYROSINE NITRATION
title_short Unraveling the effects of peroxiredoxin 2 nitration; role of C-terminal tyrosine 193
title_full Unraveling the effects of peroxiredoxin 2 nitration; role of C-terminal tyrosine 193
title_fullStr Unraveling the effects of peroxiredoxin 2 nitration; role of C-terminal tyrosine 193
title_full_unstemmed Unraveling the effects of peroxiredoxin 2 nitration; role of C-terminal tyrosine 193
title_sort Unraveling the effects of peroxiredoxin 2 nitration; role of C-terminal tyrosine 193
dc.creator.none.fl_str_mv Randall, Lía M.
Dalla Rizza, Joaquín
Parsonage, Derek
Santos, Javier
Mehl, Ryan A.
Lowther, W. Todd
Poole, Leslie B.
Denicola, Ana
author Randall, Lía M.
author_facet Randall, Lía M.
Dalla Rizza, Joaquín
Parsonage, Derek
Santos, Javier
Mehl, Ryan A.
Lowther, W. Todd
Poole, Leslie B.
Denicola, Ana
author_role author
author2 Dalla Rizza, Joaquín
Parsonage, Derek
Santos, Javier
Mehl, Ryan A.
Lowther, W. Todd
Poole, Leslie B.
Denicola, Ana
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv HYDROGEN PEROXIDE
HYPEROXIDATION
OXIDATIVE STRESS
PEROXIREDOXIN
PEROXYNITRITE
POST‐TRANSLATIONAL MODIFICATION (PTM)
REDOX SIGNALING
TYROSINE NITRATION
topic HYDROGEN PEROXIDE
HYPEROXIDATION
OXIDATIVE STRESS
PEROXIREDOXIN
PEROXYNITRITE
POST‐TRANSLATIONAL MODIFICATION (PTM)
REDOX SIGNALING
TYROSINE NITRATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Peroxiredoxins (Prx) are enzymes that efficiently reduce hydroperoxides through active participation of cysteine residues (CP, CR). The first step in catalysis, the reduction of peroxide substrate, is fast, 107 - 108 M−1s−1 for human Prx2. In addition, the high intracellular concentration of Prx positions them not only as good antioxidants but also as central players in redox signaling pathways. These biological functions can be affected by post-translational modifications that could alter the peroxidase activity and/or interaction with other proteins. In particular, inactivation by hyperoxidation of CP, which occurs when a second molecule of peroxide reacts with the CP in the sulfenic acid form, modulates their participation in redox signaling pathways. The higher sensitivity to hyperoxidation of some Prx has been related to the presence of structural motifs that disfavor disulfide formation at the active site, making the CP sulfenic acid more available for hyperoxidation or interaction with a redox protein target. We previously reported that treatment of human Prx2 with peroxynitrite results in tyrosine nitration, a post-translational modification on non-catalytic residues, yielding a more active peroxidase with higher resistance to hyperoxidation. In this work, studies on various mutants of hPrx2 confirm that the presence of the tyrosyl side-chain of Y193, belonging to the C-terminal YF motif of eukaryotic Prx, is necessary to observe the increase in Prx2 resistance to hyperoxidation. Moreover, our results underline the critical role of this structural motif on the rate of disulfide formation that determines the differential participation of Prx in redox signaling pathways.
Fil: Randall, Lía M.. Universidad de la República; Uruguay
Fil: Dalla Rizza, Joaquín. Universidad de la Republica; Uruguay
Fil: Parsonage, Derek. Wake Forest School of Medicine; Estados Unidos
Fil: Santos, Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Mehl, Ryan A.. University of Oregon; Estados Unidos
Fil: Lowther, W. Todd. Wake Forest School of Medicine; Estados Unidos
Fil: Poole, Leslie B.. Wake Forest School of Medicine; Estados Unidos
Fil: Denicola, Ana. Universidad de la República; Uruguay
description Peroxiredoxins (Prx) are enzymes that efficiently reduce hydroperoxides through active participation of cysteine residues (CP, CR). The first step in catalysis, the reduction of peroxide substrate, is fast, 107 - 108 M−1s−1 for human Prx2. In addition, the high intracellular concentration of Prx positions them not only as good antioxidants but also as central players in redox signaling pathways. These biological functions can be affected by post-translational modifications that could alter the peroxidase activity and/or interaction with other proteins. In particular, inactivation by hyperoxidation of CP, which occurs when a second molecule of peroxide reacts with the CP in the sulfenic acid form, modulates their participation in redox signaling pathways. The higher sensitivity to hyperoxidation of some Prx has been related to the presence of structural motifs that disfavor disulfide formation at the active site, making the CP sulfenic acid more available for hyperoxidation or interaction with a redox protein target. We previously reported that treatment of human Prx2 with peroxynitrite results in tyrosine nitration, a post-translational modification on non-catalytic residues, yielding a more active peroxidase with higher resistance to hyperoxidation. In this work, studies on various mutants of hPrx2 confirm that the presence of the tyrosyl side-chain of Y193, belonging to the C-terminal YF motif of eukaryotic Prx, is necessary to observe the increase in Prx2 resistance to hyperoxidation. Moreover, our results underline the critical role of this structural motif on the rate of disulfide formation that determines the differential participation of Prx in redox signaling pathways.
publishDate 2019
dc.date.none.fl_str_mv 2019-09
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/11336/162440
Randall, Lía M.; Dalla Rizza, Joaquín; Parsonage, Derek; Santos, Javier; Mehl, Ryan A.; et al.; Unraveling the effects of peroxiredoxin 2 nitration; role of C-terminal tyrosine 193; Elsevier Science Inc.; Free Radical Biology and Medicine; 141; 9-2019; 492-501
0891-5849
CONICET Digital
CONICET
url http://hdl.handle.net/11336/162440
identifier_str_mv Randall, Lía M.; Dalla Rizza, Joaquín; Parsonage, Derek; Santos, Javier; Mehl, Ryan A.; et al.; Unraveling the effects of peroxiredoxin 2 nitration; role of C-terminal tyrosine 193; Elsevier Science Inc.; Free Radical Biology and Medicine; 141; 9-2019; 492-501
0891-5849
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/S0891584919304629
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.freeradbiomed.2019.07.016
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 Science Inc.
publisher.none.fl_str_mv Elsevier Science Inc.
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 13.22299

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