| Title: |
The Catalytic Promiscuity of TSTD1-Like Sulfurtransferases Originates from a Bifaceted Active Site |
| Authors: |
Lec, Jean-Christophe; Claudel, Anne-Lise; Boutserin, Séverine; Mazon, Hortense; Mulliert, Guillermo; Boschi-Muller, Sandrine; Talfournier, François |
| Contributors: |
Ingénierie Moléculaire, Cellulaire et Physiopathologie (IMOPA); Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS); Cristallographie, Résonance Magnétique et Modélisations (CRM2) |
| Source: |
ISSN: 2155-5435. |
| Publisher Information: |
CCSD; American Chemical Society |
| Publication Year: |
2025 |
| Collection: |
Université de Lorraine: HAL |
| Subject Terms: |
Catalytic mechanism; sulfurtransferase; persulfide; catalytic promiscuity; thiosulfate; 3-mercaptopyruvate; Rhodanese fold; electrostatic contributions; [SDV]Life Sciences [q-bio] |
| Description: |
International audience ; The development of original synthesis methodologies using eco-friendly biocatalytic strategies is growing exponentially. One of the limiting factors remains the availability of efficient biocatalysts, particularly for the formation of C-S bonds. Thiosulfate sulfurtransferases (TSTs) are promising candidates that catalyze sulfur transfer from thiosulfate (TS) through the persulfide intermediate formation on the catalytic cysteine. However, the mechanism by which the sulfur-sulfur bond cleavage occurs remains to be elucidated. To address this gap of knowledge, the mechanism of persulfide formation was investigated on human TSTD1 as TST model through structure/function relationships studies. We showed that the persulfide formation by sulfur-sulfur bond cleavage of TS is critically dependent on negative charge neutralization and that the sulfur transfer process is “proton-independent”. Surprisingly, TSTD1 is more efficient in catalyzing carbon-sulfur than sulfur-sulfur bond cleavage, the former including a water-mediated protonation for which Q80 is essential. This catalytic promiscuity mainly originates from two paired residues located on opposite faces within the active site and specifically dedicated to sulfur-sulfur bond cleavage for the E31/R84 pair or carbon-sulfur bond cleavage for the Q80/R108 pair, respectively. However, we showed for other TST members that it can also be achieved through alternative catalytic strategies. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1021/acscatal.5c05390 |
| Availability: |
https://hal.univ-lorraine.fr/hal-05357177; https://doi.org/10.1021/acscatal.5c05390 |
| Accession Number: |
edsbas.5D42D7F8 |
| Database: |
BASE |