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

Roman Rohac; Patricia Amara; Alhosna Benjdia; Lydie Martin; Pauline Ruffié; Adrien Favier; Olivier Berteau; Jean-Marie Mouesca; Juan-Carlos Fontecilla-Camps; Yvain Nicolet

doi:10.1038/nchem.2490

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

Roman Rohac ¹ Patricia Amara ¹ Alhosna Benjdia ² Lydie Martin ¹ Pauline Ruffié ² Adrien Favier ¹ Olivier Berteau ² Jean-Marie Mouesca ³ Juan-Carlos Fontecilla-Camps ¹ Yvain Nicolet ¹

1 IBS - UMR 5075 - Institut de biologie structurale

2 MICALIS - MICrobiologie de l'ALImentation au Service de la Santé humaine

3 SCIB - UMR E3 - Service de Chimie Inorganique et Biologique

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.

Type de document :

Article dans une revue

Nature Chemistry, Nature Publishing Group, 2016, 8 (5), pp.491-500. <10.1038/nchem.2490>

Domaine :

Sciences du Vivant [q-bio] / Biochimie, Biologie Moléculaire / Biologie structurale [q-bio.BM]

Liste complète des métadonnées

http://hal.univ-grenoble-alpes.fr/hal-01341083
Contributeur : Frank Thomas <>
Soumis le : lundi 4 juillet 2016 - 09:57:42
Dernière modification le : mardi 21 mars 2017 - 14:12:12

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

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

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