Differential parameters between cytosolic 2-Cys peroxiredoxins, PRDX1 and PRDX2

Autores
Dalla Rizza, Joaquín; Randall, Lía M.; Santos, Javier; Ferrer Sueta, Gerardo; Denicola, Ana
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Peroxiredoxins are thiol-dependent peroxidases that function in peroxide detoxification and H2O2 induced signaling. Among the six isoforms expressed in humans, PRDX1 and PRDX2 share 97% sequence similarity, 77% sequence identity including the active site, subcellular localization (cytosolic) but they hold different biological functions albeit associated with their peroxidase activity. Using recombinant human PRDX1 and PRDX2, the kinetics of oxidation and hyperoxidation with H2O2 and peroxynitrite were followed by intrinsic fluorescence. At pH 7.4, the peroxidatic cysteine of both isoforms reacts nearly tenfold faster with H2O2 than with peroxynitrite, and both reactions are orders of magnitude faster than with most protein thiols. For both isoforms, the sulfenic acids formed are in turn oxidized by H2O2 with rate constants of ca 2 × 103 M−1 s−1 and by peroxynitrous acid significantly faster. As previously observed, a crucial difference between PRDX1 and PRDX2 is on the resolution step of the catalytic cycle, the rate of disulfide formation (11 s−1 for PRDX1, 0.2 s−1 for PRDX2, independent of the oxidant) which correlates with their different sensitivity to hyperoxidation. This kinetic pause opens different pathways on redox signaling for these isoforms. The longer lifetime of PRDX2 sulfenic acid allows it to react with other protein thiols to translate the signal via an intermediate mixed disulfide (involving its peroxidatic cysteine), whereas PRDX1 continues the cycle forming disulfide involving its resolving cysteine to function as a redox relay. In addition, the presence of C83 on PRDX1 imparts a difference on peroxidase activity upon peroxynitrite exposure that needs further study.
Fil: Dalla Rizza, Joaquín. Universidad de la Republica; Uruguay
Fil: Randall, Lía M.. Universidad de la Republica; Uruguay
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: Ferrer Sueta, Gerardo. Universidad de la Republica; Uruguay
Fil: Denicola, Ana. Universidad de la República; Uruguay
Materia
HYDROGEN PEROXIDE
HYPEROXIDATION
KINETICS
PEROXIREDOXIN 1
PEROXIREDOXIN 2
PEROXYNITRITE
REDOX SIGNALING
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:11336/130326
Acceder
id CONICETDig_fa8b084c6f2fc4836ea9e45ede05fcfd
oai_identifier_str oai:ri.conicet.gov.ar:11336/130326
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Differential parameters between cytosolic 2-Cys peroxiredoxins, PRDX1 and PRDX2Dalla Rizza, JoaquínRandall, Lía M.Santos, JavierFerrer Sueta, GerardoDenicola, AnaHYDROGEN PEROXIDEHYPEROXIDATIONKINETICSPEROXIREDOXIN 1PEROXIREDOXIN 2PEROXYNITRITEREDOX SIGNALINGhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Peroxiredoxins are thiol-dependent peroxidases that function in peroxide detoxification and H2O2 induced signaling. Among the six isoforms expressed in humans, PRDX1 and PRDX2 share 97% sequence similarity, 77% sequence identity including the active site, subcellular localization (cytosolic) but they hold different biological functions albeit associated with their peroxidase activity. Using recombinant human PRDX1 and PRDX2, the kinetics of oxidation and hyperoxidation with H2O2 and peroxynitrite were followed by intrinsic fluorescence. At pH 7.4, the peroxidatic cysteine of both isoforms reacts nearly tenfold faster with H2O2 than with peroxynitrite, and both reactions are orders of magnitude faster than with most protein thiols. For both isoforms, the sulfenic acids formed are in turn oxidized by H2O2 with rate constants of ca 2 × 103 M−1 s−1 and by peroxynitrous acid significantly faster. As previously observed, a crucial difference between PRDX1 and PRDX2 is on the resolution step of the catalytic cycle, the rate of disulfide formation (11 s−1 for PRDX1, 0.2 s−1 for PRDX2, independent of the oxidant) which correlates with their different sensitivity to hyperoxidation. This kinetic pause opens different pathways on redox signaling for these isoforms. The longer lifetime of PRDX2 sulfenic acid allows it to react with other protein thiols to translate the signal via an intermediate mixed disulfide (involving its peroxidatic cysteine), whereas PRDX1 continues the cycle forming disulfide involving its resolving cysteine to function as a redox relay. In addition, the presence of C83 on PRDX1 imparts a difference on peroxidase activity upon peroxynitrite exposure that needs further study.Fil: Dalla Rizza, Joaquín. Universidad de la Republica; UruguayFil: Randall, Lía M.. Universidad de la Republica; UruguayFil: 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: Ferrer Sueta, Gerardo. Universidad de la Republica; UruguayFil: Denicola, Ana. Universidad de la República; UruguayJohn Wiley & Sons Inc2019-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/130326Dalla Rizza, Joaquín; Randall, Lía M.; Santos, Javier; Ferrer Sueta, Gerardo; Denicola, Ana; Differential parameters between cytosolic 2-Cys peroxiredoxins, PRDX1 and PRDX2; John Wiley & Sons Inc; Protein Science; 28; 1; 1-2019; 191-2010961-8368CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1002/pro.3520info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:22:07Zoai:ri.conicet.gov.ar:11336/130326instacron: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:34982025-10-22 11:22:08.132CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Differential parameters between cytosolic 2-Cys peroxiredoxins, PRDX1 and PRDX2
title Differential parameters between cytosolic 2-Cys peroxiredoxins, PRDX1 and PRDX2
spellingShingle Differential parameters between cytosolic 2-Cys peroxiredoxins, PRDX1 and PRDX2
Dalla Rizza, Joaquín
HYDROGEN PEROXIDE
HYPEROXIDATION
KINETICS
PEROXIREDOXIN 1
PEROXIREDOXIN 2
PEROXYNITRITE
REDOX SIGNALING
title_short Differential parameters between cytosolic 2-Cys peroxiredoxins, PRDX1 and PRDX2
title_full Differential parameters between cytosolic 2-Cys peroxiredoxins, PRDX1 and PRDX2
title_fullStr Differential parameters between cytosolic 2-Cys peroxiredoxins, PRDX1 and PRDX2
title_full_unstemmed Differential parameters between cytosolic 2-Cys peroxiredoxins, PRDX1 and PRDX2
title_sort Differential parameters between cytosolic 2-Cys peroxiredoxins, PRDX1 and PRDX2
dc.creator.none.fl_str_mv Dalla Rizza, Joaquín
Randall, Lía M.
Santos, Javier
Ferrer Sueta, Gerardo
Denicola, Ana
author Dalla Rizza, Joaquín
author_facet Dalla Rizza, Joaquín
Randall, Lía M.
Santos, Javier
Ferrer Sueta, Gerardo
Denicola, Ana
author_role author
author2 Randall, Lía M.
Santos, Javier
Ferrer Sueta, Gerardo
Denicola, Ana
author2_role author
author
author
author
dc.subject.none.fl_str_mv HYDROGEN PEROXIDE
HYPEROXIDATION
KINETICS
PEROXIREDOXIN 1
PEROXIREDOXIN 2
PEROXYNITRITE
REDOX SIGNALING
topic HYDROGEN PEROXIDE
HYPEROXIDATION
KINETICS
PEROXIREDOXIN 1
PEROXIREDOXIN 2
PEROXYNITRITE
REDOX SIGNALING
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 are thiol-dependent peroxidases that function in peroxide detoxification and H2O2 induced signaling. Among the six isoforms expressed in humans, PRDX1 and PRDX2 share 97% sequence similarity, 77% sequence identity including the active site, subcellular localization (cytosolic) but they hold different biological functions albeit associated with their peroxidase activity. Using recombinant human PRDX1 and PRDX2, the kinetics of oxidation and hyperoxidation with H2O2 and peroxynitrite were followed by intrinsic fluorescence. At pH 7.4, the peroxidatic cysteine of both isoforms reacts nearly tenfold faster with H2O2 than with peroxynitrite, and both reactions are orders of magnitude faster than with most protein thiols. For both isoforms, the sulfenic acids formed are in turn oxidized by H2O2 with rate constants of ca 2 × 103 M−1 s−1 and by peroxynitrous acid significantly faster. As previously observed, a crucial difference between PRDX1 and PRDX2 is on the resolution step of the catalytic cycle, the rate of disulfide formation (11 s−1 for PRDX1, 0.2 s−1 for PRDX2, independent of the oxidant) which correlates with their different sensitivity to hyperoxidation. This kinetic pause opens different pathways on redox signaling for these isoforms. The longer lifetime of PRDX2 sulfenic acid allows it to react with other protein thiols to translate the signal via an intermediate mixed disulfide (involving its peroxidatic cysteine), whereas PRDX1 continues the cycle forming disulfide involving its resolving cysteine to function as a redox relay. In addition, the presence of C83 on PRDX1 imparts a difference on peroxidase activity upon peroxynitrite exposure that needs further study.
Fil: Dalla Rizza, Joaquín. Universidad de la Republica; Uruguay
Fil: Randall, Lía M.. Universidad de la Republica; Uruguay
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: Ferrer Sueta, Gerardo. Universidad de la Republica; Uruguay
Fil: Denicola, Ana. Universidad de la República; Uruguay
description Peroxiredoxins are thiol-dependent peroxidases that function in peroxide detoxification and H2O2 induced signaling. Among the six isoforms expressed in humans, PRDX1 and PRDX2 share 97% sequence similarity, 77% sequence identity including the active site, subcellular localization (cytosolic) but they hold different biological functions albeit associated with their peroxidase activity. Using recombinant human PRDX1 and PRDX2, the kinetics of oxidation and hyperoxidation with H2O2 and peroxynitrite were followed by intrinsic fluorescence. At pH 7.4, the peroxidatic cysteine of both isoforms reacts nearly tenfold faster with H2O2 than with peroxynitrite, and both reactions are orders of magnitude faster than with most protein thiols. For both isoforms, the sulfenic acids formed are in turn oxidized by H2O2 with rate constants of ca 2 × 103 M−1 s−1 and by peroxynitrous acid significantly faster. As previously observed, a crucial difference between PRDX1 and PRDX2 is on the resolution step of the catalytic cycle, the rate of disulfide formation (11 s−1 for PRDX1, 0.2 s−1 for PRDX2, independent of the oxidant) which correlates with their different sensitivity to hyperoxidation. This kinetic pause opens different pathways on redox signaling for these isoforms. The longer lifetime of PRDX2 sulfenic acid allows it to react with other protein thiols to translate the signal via an intermediate mixed disulfide (involving its peroxidatic cysteine), whereas PRDX1 continues the cycle forming disulfide involving its resolving cysteine to function as a redox relay. In addition, the presence of C83 on PRDX1 imparts a difference on peroxidase activity upon peroxynitrite exposure that needs further study.
publishDate 2019
dc.date.none.fl_str_mv 2019-01
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/11336/130326
Dalla Rizza, Joaquín; Randall, Lía M.; Santos, Javier; Ferrer Sueta, Gerardo; Denicola, Ana; Differential parameters between cytosolic 2-Cys peroxiredoxins, PRDX1 and PRDX2; John Wiley & Sons Inc; Protein Science; 28; 1; 1-2019; 191-201
0961-8368
CONICET Digital
CONICET
url http://hdl.handle.net/11336/130326
identifier_str_mv Dalla Rizza, Joaquín; Randall, Lía M.; Santos, Javier; Ferrer Sueta, Gerardo; Denicola, Ana; Differential parameters between cytosolic 2-Cys peroxiredoxins, PRDX1 and PRDX2; John Wiley & Sons Inc; Protein Science; 28; 1; 1-2019; 191-201
0961-8368
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1002/pro.3520
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 John Wiley & Sons Inc
publisher.none.fl_str_mv John Wiley & Sons 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
_version_ 1846781734716178432
score 12.928904

Publicaciones similares