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

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Signaling

Background:

• Protein S-sulfhydration (persulfidation) is a key H₂S signaling mechanism.
• Understanding protein modification by glutathione (GSH) is crucial for cell signaling.

Purpose of the Study:

• To investigate the novel covalent modification mechanism of S-desulfurization.
• To elucidate the role of GSH in modifying enzyme active sites.
• To explore the relationship between S-desulfurization, H₂S, and persulfidation.

Main Methods:

• Investigated modification of four enzymes (alliinase, D-LDH, ADH, G6PD) by GSH.
• Provided direct evidence for GSH-mediated S-desulfurization.
• Analyzed the mechanisms of S-desulfurization, including α-carbon nucleophilic substitution and thiol-disulfide exchange.

Main Results:

• Demonstrated that GSH binds to active cysteine sites via S-desulfurization, forming protein-SG or protein-SSG derivatives.
• Showed that S-desulfurization releases H₂S as a byproduct.
• Established S-desulfurization as the functional opposite of persulfidation, affecting H₂S levels and enzyme activity.

Conclusions:

• Elucidated the molecular mechanisms of GSH and H₂S in enzyme-metabolite systems.
• Highlighted the beneficial roles of both persulfidation and S-desulfurization in cellular processes.
• Provided a new theoretical basis for understanding GSH and H₂S in cell signaling.