Sulfur radical-induced redox modifications in proteins: analysis and mechanistic aspects.

Research paper by Christian C Schoneich

Indexed on: 12 Jun '16Published on: 12 Jun '16Published in: Antioxidants & redox signaling


The sulfur-containing amino acids cysteine (Cys) and methionine (Met) are prominent protein targets of redox modification during conditions of oxidative stress. Here, two-electron pathways have received widespread attention in part due to their role in signaling processes. However, Cys and Met are equally prone to one-electron pathways, generating intermediary radicals and/or radial ions. These radicals/radical ions can generate various reaction products which are not commonly monitored in redox proteomic studies, but may be relevant for the fate of proteins during oxidative stress.Time-resolved kinetic studies and product analysis have expanded our mechanistic understanding of radical reaction pathways of sulfur-containing amino acids. These reactions are now studied in some detail for Met and Cys in proteins, and homocysteine (Hcy) chemically linked to proteins, and a role of protein radical reactions in physiologic processes is evolving.Radical-derived products from Cys, Hcy and Met can react with additional amino acids in proteins, leading to secondary protein modifications, potentially remote from initial points of radical attack. These products may contain intra- and intermolecular cross-links, which may lead to protein aggregation. Protein sequence and conformation will have a significant impact on the formation of such products, and a thorough understanding of reaction mechanisms and specifically how protein structure influences reaction pathways will be critical for identification and characterization of novel reaction products.Future studies must evaluate the biologic significance of novel reaction products derived from radical reactions of sulfur-containing amino acids.