The missing link in COS metabolism: a model study on the reactivation of carbonic anhydrase from its hydrosulfide analogue.

Carbonic anhydrase (CA) is known to react with carbonyl sulfide, an atmospheric trace gas, whereby H2S is formed. It has been shown that, in the course of this reaction, the active catalyst, the His3ZnOH structural motif, is converted to its hydrosulfide form: His3ZnOH+COSHis3ZnSH+CO2. In this study, we elucidate the mechanism of reactivation of carbonic anhydrase (CA) from its hydrosulfide analogue by using density functional calculations, a model reaction and in vivo experimental investigation. The desulfuration occurs according to the overall equation His3ZnSH+H2O ⇌ His3ZnOH+H2S. The initial step is a protonation equilibrium at the zinc-bound hydrosulfide. The hydrogen sulfide ligand thus formed is then replaced by a water molecule, which is subsequently deprotonated to yield the reactivated catalytic centre of CA. Such a mechanism is thought to enable a plant cell to expel H2S or rapidly metabolise it to cysteine via the cysteine synthase complex. The proposed mechanism of desulfuration of the hydrosulfide analogue of CA can thus be regarded as the missing link between COS consumption of plants and their sulfur metabolism.