Por favor, use este identificador para citar o enlazar este ítem: https://hdl.handle.net/20.500.12008/56019

Título:

Kinetic and structural assessment of the reduction of human 2-Cys peroxiredoxins by thioredoxins

Otros títulos:

Coordinador:

Director:

Compilador:

Autor:

Villar, Sebastián F.
Corrales-González, Laura
Márquez de Los Santos, Belén
Dalla Rizza, Joaquín
Zeida, Ari
Denicola, Ana
Ferrer-Sueta, Gerardo

Tutor:

Tipo de documento:

Artículo

Editor:

Palabras clave:

Catalytic cycle
Hydrogen peroxide
Peroxiredoxin
Reaction mechanism
Redox signaling
Thioredoxin

Descriptores:

QUÍMICA
DISULFUROS
HUMANOS
OXIDACIÓN-REDUCCIÓN
PEROXIRREDOXINAS
METABOLISMO
COMPUESTOS DE SULFHIDRILO
TIORREDOXINAS

Año de publicación:

2024

Contenido:

Resumen:

We have studied the reduction reactions of two cytosolic human peroxiredoxins (Prx) in their disulfide form by three thioredoxins (Trx; two human and one bacterial), with the aim of better understanding the rate and mechanism of those reactions, and their relevance in the context of the catalytic cycle of Prx. We have developed a new methodology based on stopped-flow and intrinsic fluorescence to study the bimolecular reactions, and found rate constants in the range of 105 -106 m-1 s-1 in all cases, showing that there is no marked kinetic preference for the expected Trx partner. By combining experimental findings and molecular dynamics studies, we found that the reactivity of the nucleophilic cysteine (CN ) in the Trx is greatly affected by the formation of the Prx-Trx complex. The protein-protein interaction forces the CN thiolate into an unfavorable hydrophobic microenvironment that reduces its hydration and results in a remarkable acceleration of the thiol-disulfide exchange reactions by more than three orders of magnitude and also produces a measurable shift in the pKa of the CN . This mechanism of activation of the thiol disulfide exchange may help understand the reduction of Prx by alternative reductants involved in redox signaling.

Descripción:

Editorial:

Wiley; Federation of European Biochemical Societies

EN:

The FEBS Journal. 2024;291(4):778-794

Financiadores:

Citación:

Villar S, Corrales-González L, Márquez de Los Santos B y otros. Kinetic and structural assessment of the reduction of human 2-Cys peroxiredoxins by thioredoxins. The FEBS Journal [en línea]. 2024;291(4):778-794

Citación:

metadata.cc.license.name:

Documento del Gobiberno:

URI:

https://hdl.handle.net/20.500.12008/56019

ISBN:

e-ISBN:

ISSN:

ISMN:

Otros identificadores:

Título Obtenido:

Facultad o Servicio que otorga el Título:

Licencia:

Licencia Creative Commons Atribución (CC - By 4.0)

Cobertura geográfica:

Cobertura temporal:

metadata.dc.relation.IsVersionOf:

Clasificación:

Es versión de:

Colecciones:

Publicaciones Académicas y Científicas
FicherosDescripciónTamañoFormato
Kinetic and structural assessment of the reduction of human 2 Cys peroxiredoxins by thioredoxins.pdf Kinetic and structural assessment 38.65 MB Adobe PDF
Mostrar el registro Dublin Core completo del ítem