44] Labeling of protein vicinal dithiols: Role of protein-S2 to protein-(SH)2 conversion in metabolic regulation and oxidative stress

Abstract

Publisher Summary Native proteins with cysteine-sulfhydryls in proximity that can undergo reversible dithiol/disulfide conversions are here referred to as vicinal dithiol-containing proteins (VDPs). The dithiols of interest are present at the protein surface, allowing interaction with substrates, with oxidants, and with proteins catalyzing disulfide reduction. VDPs include enzymes whose active sites contain redox-active dithiols, such as nucleotide and oxidized glutathione (GSSG) reductases, thioredoxin reductase-thioredoxin, and glutaredoxin. Additionally, proteins that bind to DNA including transcription regulatory proteins with zinc fingers and most polymerases are VDPs. Also included are a series of enzymes in which the dithiol/disulfide conversion serves as an allosteric regulator of the enzymatic activity. Hormone or steroid receptors, such as the triiodothyronine nuclear receptor and the cytoplasmic glucocorticoid receptor have a dithiol that regulates hormone or steroid binding to the receptor and subsequent binding of the receptor to DNA. Another distinctive property of VDPs is their high affinity for trivalent arsenicals. This interaction is stable in the absence of other dithiols. On addition of small dithiols, such as 1,2-dithioglycerol (BAL), dithiothreitol, or lipoic acid, however, the binding of the arsenical to the dithiol protein can be reversed.