IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Unravelling the Effects of Nitration on Prx2 Peroxidase Activity
Autor/es:
RANDALL LM; SANTOS J; DENICOLA A; DALLA RIZZA J; LOWTHER; PARSONAGE D; POOLE LB
Reunión:
Congreso; Gordon Research Conference: Thiol-Based Redox Regulation and Signaling; 2018
Institución organizadora:
GRC
Resumen:
Peroxiredoxins (Prx) are a large family of thiol-dependent peroxidases that reduce hydroperoxides at expense of thioredoxin or other disulfide reductases. Prx are not only antioxidant enzymes but their extraordinary reactivity and specificity for hydroperoxides makes them ideal sensors of endogenous H2O2 and the first step in H2O2-induced signaling pathways. Prx2, a typical 2-Cys Prx, is a homodimer with a unique intermolecular redox-active disulfide center. Oxidation of the reactive Cys to sulfenic acid results in conformational changes at the active site needed for the attack of the resolving Cys to form the intermolecular disulfide. This conformational transition needed for catalysis imposes a kinetic pause that can result in reaction of the sulfenic acid with a second molecule of the oxidant substrate. This overoxidation of the peroxidatic Cys has been linked to redox signaling pathways. Post-translational modifications of Prx that could affect their activity, redox state, oligomeric structure or interaction with other proteins, will undoubtedly affect redox signaling by H2O2. Previous results of our group have shown that nitration of the enzyme with peroxynitrite renders a more active peroxidase, less sensitive to oxidative inactivation. This effect of nitration was related to a faster conformational change from the FF to the LU conformation, accelerating disulfide formation, thus increasing its peroxidase activity and preventing overoxidation. Prx2 Y193 which was nitrated belongs to the YF motif at the C-terminal associated to high susceptibility to overoxidation in eukaryotic Prx. In this work, several mutants of Prx2 tyrosine residues were assayed and compared to wild-type Prx2 and other Prx (sensitive or robust) to unravel the role of tyrosine nitration on these peroxidases.