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Publication Abstract from PubMed

We recently discovered a [Fe-S]-containing protein with in vivo thiouracil desulfidase activity called TudS. We report here the crystal structure of TudS, refined at 1.5 A resolution, which harbors a [4Fe-4S] cluster, bound by three cysteines only. Incubation of TudS crystals with 4-thiouracil trapped the cluster with a hydrosulfide ligand bound to the fourth non-protein-bonded iron, as established by the sulfur anomalous signal. This indicates that a [4Fe-5S] state of the cluster is a catalytic intermediate in the desulfuration reaction. Structural data and site-directed mutagenesis indicate that a water molecule is located next to the hydrosulfide ligand and to two catalytically important residues, Ser101 and Glu45. This information together with modeling studies allow us to propose a mechanism for the unprecedented nonredox enzymatic desulfuration of thiouracil, in which a [4Fe-4S] cluster binds and activates the sulfur atom of the substrate.

Structural evidence for a [4Fe-5S] intermediate in the non-redox desulfuration of thiouracil.,Zhou J, Pecqueur L, Aucynaite A, Fuchs J, Rutkiene R, Vaitekunas J, Meskys R, Boll M, Fontecave M, Urbonavicius J, Golinelli-Pimpaneau B Angew Chem Int Ed Engl. 2020 Sep 15. doi: 10.1002/anie.202011211. PMID:32929873^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.