INVESTIGADORES
SANTOS Javier
artículos
Título:
Differential parameters between cytosolic 2-Cys peroxiredoxins, PRDX1 and PRDX2
Autor/es:
DALLA RIZZA, JOAQUÍN; RANDALL, LÍA M.; SANTOS, JAVIER; FERRER-SUETA, GERARDO; DENICOLA, ANA
Revista:
PROTEIN SCIENCE
Editorial:
JOHN WILEY & SONS INC
Referencias:
Año: 2019 vol. 28 p. 191 - 201
ISSN:
0961-8368
Resumen:
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.