Signalling by hydrogen sulfide and polysulfides via protein S-sulfuration

Hydrogen sulfide (H₂ S) is a signalling molecule that regulates neuronal transmission, vascular tone, cytoprotection, inflammatory responses, angiogenesis, and oxygen sensing. Some of these functions have recently been ascribed to its oxidized form polysulfides (H₂ S_n ), which can be produced by 3-mercaptopyruvate sulfurtransferase (MPST), also known as a H₂ S-producing enzyme. H₂ S_n activate ion channels, tumour suppressors, transcription factors, and protein kinases. H₂ S_n S-sulfurate (S-sulfhydrate) cysteine residues of these target proteins to modify their activity by inducing conformational changes through the formation of a disulfide bridge between the two cysteine residues involved. The chemical interaction between H₂ S and NO also generates H₂ S_n , which may be a chemical entity that exerts the synergistic effect of H₂ S and NO. MPST also produces redox regulators cysteine persulfide (CysSSH), GSH persulfide (GSSH), and persulfurated proteins. In addition to MPST, haemoproteins such as haemoglobin, myoglobin, neuroglobin, and catalase as well as SOD can produce H₂ S_n , and sulfide quinone oxidoreductase and cysteinyl tRNA synthetase can make GSSH and CysSSH. This review focuses on the recent progress in the study of the production and physiological roles of these persulfurated and polysulfurated molecules. LINKED ARTICLES: This article is part of a themed section on Hydrogen Sulfide in Biology & Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.4/issuetoc.