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The glyceraldehyde-3-phosphate dehydrogenase GapDH of Corynebacterium diphtheriae is redox-controlled by protein S-mycothiolation under oxidative stress
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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5504048/ https://www.ncbi.nlm.nih.gov/pubmed/28694441 http://dx.doi.org/10.1038/s41598-017-05206-2 |
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author | Hillion, Melanie Imber, Marcel Pedre, Brandán Bernhardt, Jörg Saleh, Malek Loi, Vu Van Maaß, Sandra Becher, Dörte Astolfi Rosado, Leonardo Adrian, Lorenz Weise, Christoph Hell, Rüdiger Wirtz, Markus Messens, Joris Antelmann, Haike |
author_facet | Hillion, Melanie Imber, Marcel Pedre, Brandán Bernhardt, Jörg Saleh, Malek Loi, Vu Van Maaß, Sandra Becher, Dörte Astolfi Rosado, Leonardo Adrian, Lorenz Weise, Christoph Hell, Rüdiger Wirtz, Markus Messens, Joris Antelmann, Haike |
author_sort | Hillion, Melanie |
collection | PubMed |
description | 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 H(2)O(2) and NaOCl resulted in irreversible inactivation due to overoxidation of the active site in vitro. Treatment of GapDH with H(2)O(2) 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. |
format | Online Article Text |
id | pubmed-5504048 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-55040482017-07-12 The glyceraldehyde-3-phosphate dehydrogenase GapDH of Corynebacterium diphtheriae is redox-controlled by protein S-mycothiolation under oxidative stress Hillion, Melanie Imber, Marcel Pedre, Brandán Bernhardt, Jörg Saleh, Malek Loi, Vu Van Maaß, Sandra Becher, Dörte Astolfi Rosado, Leonardo Adrian, Lorenz Weise, Christoph Hell, Rüdiger Wirtz, Markus Messens, Joris Antelmann, Haike Sci Rep Article 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 H(2)O(2) and NaOCl resulted in irreversible inactivation due to overoxidation of the active site in vitro. Treatment of GapDH with H(2)O(2) 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. Nature Publishing Group UK 2017-07-10 /pmc/articles/PMC5504048/ /pubmed/28694441 http://dx.doi.org/10.1038/s41598-017-05206-2 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Hillion, Melanie Imber, Marcel Pedre, Brandán Bernhardt, Jörg Saleh, Malek Loi, Vu Van Maaß, Sandra Becher, Dörte Astolfi Rosado, Leonardo Adrian, Lorenz Weise, Christoph Hell, Rüdiger Wirtz, Markus Messens, Joris Antelmann, Haike The glyceraldehyde-3-phosphate dehydrogenase GapDH of Corynebacterium diphtheriae is redox-controlled by protein S-mycothiolation under oxidative stress |
title | The glyceraldehyde-3-phosphate dehydrogenase GapDH of Corynebacterium diphtheriae is redox-controlled by protein S-mycothiolation under oxidative stress |
title_full | The glyceraldehyde-3-phosphate dehydrogenase GapDH of Corynebacterium diphtheriae is redox-controlled by protein S-mycothiolation under oxidative stress |
title_fullStr | The glyceraldehyde-3-phosphate dehydrogenase GapDH of Corynebacterium diphtheriae is redox-controlled by protein S-mycothiolation under oxidative stress |
title_full_unstemmed | The glyceraldehyde-3-phosphate dehydrogenase GapDH of Corynebacterium diphtheriae is redox-controlled by protein S-mycothiolation under oxidative stress |
title_short | The glyceraldehyde-3-phosphate dehydrogenase GapDH of Corynebacterium diphtheriae is redox-controlled by protein S-mycothiolation under oxidative stress |
title_sort | glyceraldehyde-3-phosphate dehydrogenase gapdh of corynebacterium diphtheriae is redox-controlled by protein s-mycothiolation under oxidative stress |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5504048/ https://www.ncbi.nlm.nih.gov/pubmed/28694441 http://dx.doi.org/10.1038/s41598-017-05206-2 |
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