Quantification of Protein Sulfenic Acid Modifications Using Isotope-Goded Dimedone and Iododimedone

摘要

Since its discovery almost 40 years ago, S-hydroxylation (—SOH) of cysteine thiol side chains at active and allosteric sites within proteins has emerged as a central post-transla-tional modification.At present, more than 200 transcription factors, signaling proteins, metabolic enzymes, proteostasis regulators, and cytoskeletal components that undergo sulfenic acid modification have been identified. Like phosphorylation, S-hydroxylation can be a dynamic and reversible post-translational modification whereby hydrogen peroxide (H2O2) and other reactive oxygen species (ROS) generated during the "oxidative burst" that accompanies many receptor-mediated signaling processes react with a thiolate anion to form sulfenic acid, and a family of enzymes reduces these modifications (or subsequent disulfides) in proteins (Scheme 1). Although protein sulfenic acids are often transient and labile, S-hydroxylation is significant in physiological and pathophysiological events. For example, it has been shown that this modification plays an essential role in eukaryotic H2O2 sensing, T-cell activation, enzyme catalysis, as an intermediate in disulfide formation, and correlates with disease states.