rhodaneses

Rhodaneses, or thiosulfate sulfurtransferases, are a family of enzymes that catalyze the transfer of a sulfur atom from a donor to an acceptor substrate. The best known member is rhodanese, which converts thiosulfate and cyanide into sulfite and thiocyanate. In humans, the mitochondrial enzyme is encoded by the TST gene and contributes to cellular sulfur trafficking and detoxification.

Biological role and substrates are diverse. The canonical reaction involves cyanide detoxification, converting CN− to the less toxic thiocyanate, while enabling the regeneration of the active site. Beyond cyanide handling, rhodanese and rhodanese-like domains participate in broader sulfur transfer processes, moving sulfane sulfur to various acceptors as part of sulfur metabolism and homeostasis. Many organisms rely on rhodanese activity to manage reactive sulfur species and to support mitochondrial function.

Mechanism and structure. Rhodaneses operate via a ping-pong mechanism in which a catalytic cysteine forms a persulfide intermediate. The sulfur is first transferred from thiosulfate to the active-site cysteine, releasing sulfite, and then transferred to another substrate (such as cyanide) to form thiocyanate and reconstitute the enzyme. Structurally, rhodaneses are typically two-domain proteins, with the active site located at the interface between domains. The rhodanese fold (RHD) is also found as a conserved domain in many other proteins, reflecting a broader role in sulfur transfer beyond classical rhodanese.

Distribution and evolution. Rhodanese and rhodanese-like domains are widespread across bacteria, archaea, and eukaryotes. Gene families and multidomain proteins incorporating RHDs illustrate the evolutionary expansion of sulfurtransfer chemistry, linking metabolism to detoxification and redox regulation.