6Z96

[4Fe-4S]-dependent thiouracil desulfidase TudS (DUF523Vcz) soaked with 4-thiouracil (12.65 keV, 7.125 keV (Fe-SAD) and 6.5 keV (S-SAD) data)

Summary for 6Z96

• Entry DOI: 10.2210/pdb6z96/pdb
• Related: 6Z92 6Z93 6Z94 6Z95
• Descriptor: TudS, IRON/SULFUR CLUSTER, HYDROSULFURIC ACID, ... (6 entities in total)
• Functional Keywords: thiouracil, iron-sulfur cluster, desulfuration, sulfurtransferase, transferase
• Biological source: uncultured bacterium
• Total number of polymer chains: 2
• Total formula weight: 36331.84

Authors

Pecqueur, L.,Zhou, J.,Fontecave, M.,Golinelli-Pimpaneau, B. (deposition date: 2020-06-03, release date: 2020-09-30, Last modification date: 2024-01-24)

Primary citation

Zhou, J.,Pecqueur, L.,Aucynaite, A.,Fuchs, J.,Rutkiene, R.,Vaitekunas, J.,Meskys, R.,Boll, M.,Fontecave, M.,Urbonavicius, J.,Golinelli-Pimpaneau, B.
Structural Evidence for a [4Fe-5S] Intermediate in the Non-Redox Desulfuration of Thiouracil.
Angew.Chem.Int.Ed.Engl., 60:424-431, 2021

PubMed Abstract: We recently discovered a [Fe-S]-containing protein with in vivo thiouracil desulfidase activity, dubbed TudS. The crystal structure of TudS refined at 1.5 Å resolution is reported; it 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 non-redox enzymatic desulfuration of thiouracil, in which a [4Fe-4S] cluster binds and activates the sulfur atom of the substrate.

PubMed: 32929873
DOI: 10.1002/anie.202011211

Experimental method

X-RAY DIFFRACTION (1.327 Å)