TtuA and TudS, two [4Fe-4S]-dependent enzymes catalyzing non-redox sulfuration or desulfuration reactions

International audienceU54-tRNA sulfurtransferase TtuA and thiouracil desulfidase TudS catalyze two opposite reactions that necessitate a [4Fe-4S] cluster: non-redox sulfuration or desulfuration reactions. On the one hand, TtuA is an ATPdependent sulfurtransferase (thiouridine synthase) that transfers a sulfur atom, originating from free L-cysteine, to uridine at position 54 within the T-loop of tRNAs in thermophilic organisms. In some cases, thiouridine biosynthesis involves a sulfur transfer between a thiocarboxylate formed at the C-terminal glycine of a TtuB protein and the [4Fe-4S] cluster of TtuA, within a TtuA/TtuB complex. On the other hand, TudS catalyzes sulfur abstraction from its 2-thiouracil or 4thiouracil substrate. Interestingly, in both reactions, the [4Fe-4S] cluster, bound to three cysteines only, is presumably used as a cofactor to bind and activate a sulfur atom, coming from a sulfur donor for TtuA or from the thiouracil substrate for TudS. Therefore, catalysis most probably occurs via the formation of a [4Fe-4S] cluster-bound sulfide intermediate, as illustrated by the [4Fe-5S] cluster state that was trapped by soaking crystals of TudS with the 4-thiouracil substrate