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Carbon-sulfur bond-forming reaction catalysed by the radical SAM enzyme HydE.
- Source :
-
Nature chemistry [Nat Chem] 2016 May; Vol. 8 (5), pp. 491-500. Date of Electronic Publication: 2016 Apr 04. - Publication Year :
- 2016
-
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.
- Subjects :
- Carbon chemistry
Catalysis
Catalytic Domain
Clostridium acetobutylicum enzymology
Cysteine analogs & derivatives
Cysteine chemistry
Free Radicals chemistry
Ligands
Models, Chemical
Quantum Theory
S-Adenosylmethionine chemistry
Sulfur chemistry
Thermotoga maritima enzymology
Oxidoreductases Acting on Sulfur Group Donors chemistry
Thiazolidines chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1755-4349
- Volume :
- 8
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Nature chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 27102684
- Full Text :
- https://doi.org/10.1038/nchem.2490