The glyceraldehyde-3-phosphate dehydrogenase GapDH of Corynebacterium diphtheriae is redox-controlled by protein S-mycothiolation under oxidative stress.

TitleThe glyceraldehyde-3-phosphate dehydrogenase GapDH of Corynebacterium diphtheriae is redox-controlled by protein S-mycothiolation under oxidative stress.
Publication TypeJournal Article
Year of Publication2017
AuthorsHillion, M., M. Imber, B. Pedre, J. Bernhardt, M. Saleh, V. Van Loi, S. MaaƟ, D. Becher, L. Astolfi Rosado, L. Adrian, C. Weise, R. Hell, M. Wirtz, J. Messens, and H. Antelmann
JournalSci Rep
Volume7
Issue1
Pagination5020
Date Published2017 Jul 10
ISSN2045-2322
Abstract

Mycothiol (MSH) is the major low molecular weight (LMW) thiol in Actinomycetes and functions in post-translational thiol-modification by protein S-mycothiolation as emerging thiol-protection and redox-regulatory mechanism. Here, we have used shotgun-proteomics to identify 26 S-mycothiolated proteins in the pathogen Corynebacterium diphtheriae 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 S-mycothiolated protein that was modified at its active site Cys153 in vivo. Exposure of purified GapDH to HO and NaOCl resulted in irreversible inactivation due to overoxidation of the active site in vitro. Treatment of GapDH with HO or NaOCl in the presence of MSH resulted in S-mycothiolation and reversible GapDH inactivation in vitro which was faster compared to the overoxidation pathway. Reactivation of S-mycothiolated GapDH could be catalyzed by both, the Trx and the Mrx1 pathways in vitro, but demycothiolation by Mrx1 was faster compared to Trx. In summary, we show here that S-mycothiolation can function in redox-regulation and protection of the GapDH active site against overoxidation in C. diphtheriae which can be reversed by both, the Mrx1 and Trx pathways.

DOI10.1038/s41598-017-05206-2
Alternate JournalSci Rep
PubMed ID28694441
PubMed Central IDPMC5504048
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