The sulfhydryl (-SH) group in the side chain of cysteine residues in protein is subject to several post-translational modification types, including sulphenation (-SOH), sulphination (-SO2H), nitrosylation (-SNO), sulfhydration (-SSH), glutathionylation, and adduction to endogenous and exogenous electrophiles. Adduction of fumarate to the free sulfhydryl group (succination) of certain cysteine residues in protein results in the formation of S-(2-succino)cysteine (2SC) sites. Originally discovered in plasma proteins, including albumin, this modification type has been implicated in the pathogenesis of diabetes/obesity and fumarate hydratase-associated diseases. Experimental identification of modified sites is typically a labor-intensive and expensive approach. Computational prediction of these sites could be a convenient and high-throughput strategy to generate helpful information for subsequent experimental verification. Until now, no method has been specifically developed to investigate protein succination. By analyzing the “succinate proteome”, aim of this Project is to develop computational methods to predict 2SC sites in proteins.
Protein succination; cysteine; fumarate