Carbon-sulfur bond-forming reaction catalysed by the radical SAM enzyme HydE.

Abstract : 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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Article dans une revue
Nature Chemistry, Nature Publishing Group, 2016, 8 (5), pp.491-500. 〈10.1038/nchem.2490〉
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http://hal.univ-grenoble-alpes.fr/hal-01341083
Contributeur : Frank Thomas <>
Soumis le : lundi 4 juillet 2016 - 09:57:42
Dernière modification le : vendredi 9 mars 2018 - 16:36:02

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Roman Rohac, Patricia Amara, Alhosna Benjdia, Lydie Martin, Pauline Ruffié, et al.. Carbon-sulfur bond-forming reaction catalysed by the radical SAM enzyme HydE.. Nature Chemistry, Nature Publishing Group, 2016, 8 (5), pp.491-500. 〈10.1038/nchem.2490〉. 〈hal-01341083〉

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