5FEP

HydE from T. maritima in complex with (2R,4R)-MeTDA

Summary for 5FEP

• Entry DOI: 10.2210/pdb5fep/pdb
• Related: 3IIX 3IIZ
• Descriptor: [FeFe] hydrogenase maturase subunit HydE, IRON/SULFUR CLUSTER, 3-[(3-CHOLAMIDOPROPYL)DIMETHYLAMMONIO]-1-PROPANESULFONATE, ... (7 entities in total)
• Functional Keywords: radical sam enzyme, complex, fefe-hydrogenase maturase, oxidoreductase
• Biological source: Thermotoga maritima
• Total number of polymer chains: 1
• Total formula weight: 45076.50

Authors

Rohac, R.,Amara, P.,Benjdia, A.,Martin, L.,Ruffie, P.,Favier, A.,Berteau, O.,Mouesca, J.M.,Fontecilla-Camps, J.C.,Nicolet, Y. (deposition date: 2015-12-17, release date: 2016-04-06, Last modification date: 2024-01-10)

Primary citation

Rohac, R.,Amara, P.,Benjdia, A.,Martin, L.,Ruffie, P.,Favier, A.,Berteau, O.,Mouesca, J.M.,Fontecilla-Camps, J.C.,Nicolet, Y.
Carbon-sulfur bond-forming reaction catalysed by the radical SAM enzyme HydE.
Nat.Chem., 8:491-500, 2016

PubMed 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.

PubMed: 27102684
DOI: 10.1038/nchem.2490

Experimental method

X-RAY DIFFRACTION (1.45 Å)