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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/162440
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CONICET Digital (CONICET) |
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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 Técnicas2025-09-29T10:09:27Zoai: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:34982025-09-29 10:09:27.734CONICET 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 |
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CONICET Digital (CONICET) |
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CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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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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1844613973639430144 |
score |
13.070432 |