Hydrogen sulfide (H2S) is best known for its characteristic smell of rotten eggs and for its toxicity, which is caused mainly by inhibition of mitochondrial respiration resulting from blockade of cytochrome oxidase. More recently, H2S has been established as one of a number of gaseous signalling molecules, with roles in neuromodulation, smooth muscle relaxation, inflammation, insulin release and metabolic demand. Although biochemical pathways which generate H2S have been elucidated, exactly what it does once generated has been unclear. Writing in the journal Science Signalling, a team led by researchers at Johns Hopkins University School of Medicine have now shown that H2S converts cysteine residues to thiocysteines (ie modifies the –SH group to –SSH) in many liver proteins, including actin, tubulin, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Interestingly, the cysteine residue in GAPDH that is modified to thiocysteine (Cys150) is also a target of nitrosylation by nitric oxide (NO), another gaseous signalling molecule. Nitrosylation of the cysteine residue abolishes GAPDH activity, whereas conversion to thiocysteine augments activity, suggesting that the function of some proteins could be regulated by competitive nitrosylation or sulfhydration of the same cysteine residues. The extent of sulfhydration (10-25%) is considerably higher than the degree of protein S-nitrosylation thought to occur physiologically.