The glyceraldehyde-3-phosphate dehydrogenase GapDH of Corynebacterium diphtheriae is redox-controlled by protein S-mycothiolation under oxidative stress
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The glyceraldehyde-3-phosphate dehydrogenase GapDH of Corynebacterium diphtheriae is redox-controlled by protein S-mycothiolation under oxidative stress
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<jats:title>Abstract</jats:title><jats:p>Mycothiol (MSH) is the major low molecular weight (LMW) thiol in Actinomycetes and functions in post-translational thiol-modification by protein <jats:italic>S</jats:italic>-mycothiolation as emerging thiol-protection and redox-regulatory mechanism. Here, we have used shotgun-proteomics to identify 26 <jats:italic>S</jats:italic>-mycothiolated proteins in the pathogen <jats:italic>Corynebacterium diphtheriae</jats:italic> DSM43989 under hypochlorite stress that are involved in energy metabolism, amino acid and nucleotide biosynthesis, antioxidant functions and translation. The glyceraldehyde-3-phosphate dehydrogenase (GapDH) represents the most abundant <jats:italic>S</jats:italic>-mycothiolated protein that was modified at its active site Cys153 <jats:italic>in vivo</jats:italic>. Exposure of purified GapDH to H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub> and NaOCl resulted in irreversible inactivation due to overoxidation of the active site <jats:italic>in vitro</jats:italic>. Treatment of GapDH with H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub> or NaOCl in the presence of MSH resulted in <jats:italic>S</jats:italic>-mycothiolation and reversible GapDH inactivation <jats:italic>in vitro</jats:italic> which was faster compared to the overoxidation pathway. Reactivation of <jats:italic>S</jats:italic>-mycothiolated GapDH could be catalyzed by both, the Trx and the Mrx1 pathways <jats:italic>in vitro</jats:italic>, but demycothiolation by Mrx1 was faster compared to Trx. In summary, we show here that <jats:italic>S</jats:italic>-mycothiolation can function in redox-regulation and protection of the GapDH active site against overoxidation in <jats:italic>C</jats:italic>. <jats:italic>diphtheriae</jats:italic> which can be reversed by both, the Mrx1 and Trx pathways.</jats:p>