Société Française de Biochimie et Biologie Moléculaire

Jean-Christophe Lec - June 2018

IMoPA, UMR 7365 CNRS-University of Lorraine, Vandoeuvre-lès-Nancy Unraveling the Mechanism of Cysteine Persulfide Formation Catalyzed by 3-Mercaptopyruvate Sulfurtransferases 2018, ACS Catalysis, 8, 2049–2059. DOI : 10.1021/acscatal.7b02432 Jean-Christophe Lec, Séverine Boutserin, Hortense Mazon, Guillermo Mulliert, Sandrine Boschi-Muller, and François Talfournier


Jean-Christophe Lec, 28 years old, obtained a degree in biochemistry from the University of Franche-Comté and a Master's degree in molecular engineering from the University of Lorraine. He completed his thesis in three years under the co-direction of Prof. Sandrine Boschi-Muller and Dr. François Talfournier at the IMoPA laboratory. The objective of his project was to decipher the molecular mechanisms implicating thioltransferases with rhodanese domain in order to better understand their physiological roles. His thesis work describes the catalytic mechanism of persulfide formation. The demonstration of such a mechanism is of great interest in hydrogen sulfide enzymology field because persulfides are known to mediate the H2S-dependent signalling.


Jean-Christophe LEC, PhD.
Engineer Maturation
SATT Grand-Est

Laboratoire IMoPA UMR 7365
Equipe 3 : Enzymologie Moléculaire et Structurale
9 Avenue de la forêt de Haye
Bâtiment Biopole


Sulfhydration of reactive cysteines in target proteins is now recognized as a major route by which H2S mediates signal transduction and regulates various cellular processes. Among the enzymatic systems permitting the formation of cysteine persulfide from nonactivated sulfur compounds, 3-mercaptopyruvate sulfurtransferases can be considered as a model of thiolate-based chemistry for carbon–sulfur bond breaking. These ubiquitous enzymes transfer a sulfur atom from 3-mercaptopyruvate (3-MP) to a thiol acceptor via a cysteine-persulfide intermediate, but the mechanistic basis for its formation is still unclear. To address this question, kinetic approaches were developed for studying the reaction catalyzed by the human and Escherichia coli enzymes and the role of several conserved residues was also investigated. We showed that the first step of sulfur transfer that leads to pyruvate release and formation of the persulfide intermediate is very efficient for both enzymes. It critically depends on the electrostatic contribution provided by the CGSGVT catalytic loop, while any role of the so-called Ser/His/Asp triad can be excluded. Furthermore, solvent kinetic isotopic effect and proton inventory studies revealed a concerted mechanism in which the water-mediated protonation of the pyruvate enolate and S0 transfer from the deprotonated 3-MP to the thiolate form of the catalytic cysteine occur concomitantly.