S-desulfurization: A different covalent modification mechanism from persulfidation by GSH.

Post-translational transformation of cysteine residues to persulfides, known as protein S-sulfhydration or persulfidation, is a beneficial H 2 S signaling mechanism. In this paper, we found that GSH is bound to active cysteine sites of protein by S-desulfurization, which is a new covalent modification mechanism of protein, thus regulating catalytic activity. Here, we provide direct evidence that GSH modifies the reactive cysteine residues of four enzymes (alliinase/ D -LDH/ADH/G6PD) and generates protein-SG or protein-SSG derivatives by S-desulfurization. S-desulfurization, α-carbon nucleophilic substitution or thiol-disulfide exchange occurs and H 2 S is released as a by-product. S-desulfurization is the opposite of persulfidation in terms of H 2 S production/consumption and enzyme inhibition/mitigation. Here, we elucidated the GSH mechanisms and H 2 S mechanisms in the enzyme-metabolite system and the beneficial roles of persulfidation and S-desulfurization. These theoretical findings are now shedding light on understanding GSH and H 2 S molecular functions and providing new theoretical basis for them in cell signaling pathways. [Display omitted] • GSH-modified proteins forming protein-SG derivatives is named S-desulfurization. • S-desulfurization is a protein modification mechanism with a sulfur atom minus. • Moderate GSH concentrations alleviate inactivation against persulfidation. • Persulfidation of DADS/DATS/allicin is an enzyme-metabolite protection. [ABSTRACT FROM AUTHOR]