Alexandre Kriznik, research engineer, UMS technical head and PhD student in the Molecular Enzymology team of the IMoPA laboratory, defended his thesis on June 22, amphi Gallé, Presidency Brabois of the University of Lorraine.

Here is a summary of his thesis work:

Peroxiredoxins from the Prx1 subfamily (Prx) are moonlighting peroxidases that operate in peroxide signaling and are regulated by sulfinylation. Prxs offer a major model of protein−thiol oxidative modification. They react with H2O2 to form a sulfenic acid intermediate that can be sulfenylated. Sensitivity of to sulfinylation determines the role of Prx in redox signaling, antioxidant response or as chaperones. Prx sulfinylation sensitivity depends is critically influenced by a structural transition from a fully folded (FF) to locally unfolded (LU) conformation. This study has required the development of fine kinetic methods of the fast kinetic type, coupled with biophysical techniques such as circular dichroism and fluorescence spectroscopy. Analysis of the reaction of the Tsa1 Saccharomyces cerevisiae Prx with H2O2 revealed a process linked to the FF/LU transition that is kinetically distinct from disulfide formation and suggested that sulfenate formation facilitates local unfolding. Use of mutants of distinctive sensitivities and of different peroxide substrates showed that sulfinylation sensitivity depends only on the sulfenic acid oxidation and FF-to-LU transition rate constants. From these two parameters, the relative sensitivities of Prxs toward hyperoxidation with different substrates can be predicted, as confirmed by in vitro and in vivo patterns.

Publication: Kriznik A, Libiad M, Le Cordier H, Boukhenouna S, Toledano MB, Rahuel-Clermont S. Dynamics of a key conformational transition in the mechanism of peroxiredoxin sulfinylation. ACS Catalysis. 2020. DOI : 10.1021/acscatal.9b04471