H₂S-Mediated Protein S-Sulfhydration: A Prediction for Its Formation and Regulation

Protein -sulfhydration is a newly discovered post-translational modification of specific cysteine residue(s) in target proteins, which is involved in a broad range of cellular functions and metabolic pathways. By changing local conformation and the final activity of target proteins, -sulfhydration is believed to mediate most cellular responses initiated by H₂S, a novel gasotransmitter. In comparison to protein -sulfhydration, nitric oxide-mediated protein -nitrosylation has been extensively investigated, including its formation, regulation, transfer and metabolism. Although the investigation on the regulatory mechanisms associated with protein -sulfhydration is still in its infancy, accumulated evidence suggested that protein -sulfhydration may share similar chemical features with protein -nitrosylation. Glutathione persulfide acts as a major donor for protein -sulfhydration. Here, we review the present knowledge on protein -sulfhydration, and also predict its formation and regulation mechanisms based on the knowledge from protein -nitrosylation.