Journal
NATURE CHEMISTRY
Volume 8, Issue 5, Pages 491-500Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/NCHEM.2490
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Funding
- French Agence Nationale pour la Recherche [ANR-12-BSV8-0013]
- FRISBI within the Grenoble Partnership for Structural Biology [ANR-10-INSB-05-02]
- 'Irtelis' Fellowship from the CEA
- Agence Nationale de la Recherche (ANR) [ANR-12-BSV8-0013] Funding Source: Agence Nationale de la Recherche (ANR)
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Carbon-sulfur bond formation at aliphatic positions is a challenging reaction that is performed efficiently by radical S-adenosyl-L-methionine (SAM) enzymes. Here we report that 1,3-thiazolidines can act as ligands and substrates for the radical SAM enzyme HydE, which is involved in the assembly of the active site of [FeFe]-hydrogenase. Using X-ray crystallography, in vitro assays and NMR spectroscopy we identified a radical-based reaction mechanism that is best described as the formation of a C-centred radical that concomitantly attacks the sulfur atom of a thioether. To the best of our knowledge, this is the first example of a radical SAM enzyme that reacts directly on a sulfur atom instead of abstracting a hydrogen atom. Using theoretical calculations based on our high-resolution structures we followed the evolution of the electronic structure from SAM through to the formation of S-adenosyl-L-cysteine. Our results suggest that, at least in this case, the widely proposed and highly reactive 5'-deoxyadenosyl radical species that triggers the reaction in radical SAM enzymes is not an isolable intermediate.
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