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Nat Chem. 2016 May;8(5):491-500. doi: 10.1038/nchem.2490. Epub 2016 Apr 4.

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

Author information

1
Metalloproteins Unit, Institut de Biologie Structurale, CEA, CNRS, UGA, 71 Avenue des Martyrs, 38044 Grenoble Cedex 9, France.
2
Micalis Institute, ChemSyBio, INRA, AgroParisTech, Université Paris-Saclay, F-78350 Jouy-en-Josas, France.
3
Biomolecular NMR Spectroscopy Group, Institut de Biologie Structurale, CEA, CNRS, UGA, 71 Avenue des Martyrs, 38044 Grenoble Cedex 9, France.
4
Université Grenoble Alpes, INAC, SCIB/LRM, F-38000 Grenoble, France.
5
CEA, INAC, SCIB/LRM, F-38054 Grenoble, France.

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.

PMID:
27102684
DOI:
10.1038/nchem.2490
[Indexed for MEDLINE]

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