Skip to Main content Skip to Navigation

Les thioltransférases, des agents doubles impliqués dans le métabolisme du sulfure d’hydrogène : de la catalyse aux rôles physiologiques

Abstract : 3-mercaptopyruvate sulfurtransferases (3-MSTs) and thiosulfate sulfurtransferases (TSTs) are ubiquitous enzymes that belong to the rhodanese sulfurtransferase family and catalyze the transfer of a sulfur atom from a donor to an acceptor substrate via a cysteine-persulfide intermediate. While 3-MSTs are involved in the biogenesis of hydrogen sulfide (H2S), a gasotransmitter known to be toxic at high concentration, TSTs are likely responsible of its degradation. My project mainly focused on deciphering the sulfurtransferase-dependent molecular mechanisms to better define their physiological functions. To address these questions, their catalytic mechanisms and substrate specificities were investigated. This was achieved through the development of kinetic approaches (fluorescence, stopped-flow, H2S specific probe) to study each step of the reaction catalyzed by human (3-MST, TSTD1 and Rhodanese) and Escherichia coli (3-MST, GlpE) enzymes and structure-function relationship studies performed in collaboration for the theoretical chemistry and the X-ray crystallography parts. Here, I show that the active site of these enzymes is optimized to perform an efficient S0 transfer from non-activated sulfur compounds. Moreover, the mechanisms leading to formation of the persulfide intermediate do not depend on the enzyme but rather on the donor substrate. Indeed, the cleavage of the carbon-sulfur bond of 3-mercaptopyruvate critically depends on the CysX5 catalytic loop acting as a thiolate hole to favor the deprotonation of the essential Cys and the substrate, and on a water-mediated protonation step. In the presence of thiosulfate, the Cys activation mode remains unchanged and the reaction of sulfur transfer is only driven by the neutralization of the negative charges of the substrate. In addition, we propose a new physiological function for the human 3-MST in the cytoplasmic elimination of sulfite, a toxic compound for the cells. Finally, the two human mitochondrial TSTs are likely to be involved in the H2S-mediated cellular signaling, through the formation of polysulfide entities, but also in H2S catabolism
Document type :
Complete list of metadata

Cited literature [240 references]  Display  Hide  Download
Contributor : Thèses UL Connect in order to contact the contributor
Submitted on : Wednesday, November 18, 2020 - 4:44:53 PM
Last modification on : Wednesday, November 3, 2021 - 4:47:03 AM
Long-term archiving on: : Friday, February 19, 2021 - 8:21:11 PM


Files produced by the author(s)


  • HAL Id : tel-01934624, version 1


Jean-Christophe Lec. Les thioltransférases, des agents doubles impliqués dans le métabolisme du sulfure d’hydrogène : de la catalyse aux rôles physiologiques. Biochimie, Biologie Moléculaire. Université de Lorraine, 2017. Français. ⟨NNT : 2017LORR0305⟩. ⟨tel-01934624⟩



Record views


Files downloads