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Mol Cell Biochem. 2019 Aug 2. doi: 10.1007/s11010-019-03593-w. [Epub ahead of print]

A key metabolic integrator, coenzyme A, modulates the activity of peroxiredoxin 5 via covalent modification.

Author information

1
Department of Structural and Molecular Biology, University College London, London, WC1E 6BT, UK.
2
Biological Mass Spectrometry & Proteomics Cell Biology, MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK.
3
Department of Oral Biochemistry and Department of Molecular Medicine (BK21plus), Dental Science Research Institute, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.
4
Department of Cell and Developmental Biology, University College London, London, WC1E 6BT, UK.
5
Bloomsbury Institute of Intensive Care Medicine, University College London, London, WC1E 6BT, UK.
6
Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv, 03680, Ukraine.
7
Department of Structural and Molecular Biology, University College London, London, WC1E 6BT, UK. i.gout@ucl.ac.uk.

Abstract

Peroxiredoxins (Prdxs) are antioxidant enzymes that catalyse the breakdown of peroxides and regulate redox activity in the cell. Peroxiredoxin 5 (Prdx5) is a unique member of Prdxs, which displays a wider subcellular distribution and substrate specificity and exhibits a different catalytic mechanism when compared to other members of the family. Here, the role of a key metabolic integrator coenzyme A (CoA) in modulating the activity of Prdx5 was investigated. We report for the first time a novel mode of Prdx5 regulation mediated via covalent and reversible attachment of CoA (CoAlation) in cellular response to oxidative and metabolic stress. The site of CoAlation in endogenous Prdx5 was mapped by mass spectrometry to peroxidatic cysteine 48. By employing an in vitro CoAlation assay, we showed that Prdx5 peroxidase activity is inhibited by covalent interaction with CoA in a dithiothreitol-sensitive manner. Collectively, these results reveal that human Prdx5 is a substrate for CoAlation in vitro and in vivo, and provide new insight into metabolic control of redox status in mammalian cells.

KEYWORDS:

Coenzyme A (CoA); Oxidative stress; Peroxiredoxin 5 (Prdx5); Reactive oxygen species (ROS); Redox regulation

PMID:
31375973
DOI:
10.1007/s11010-019-03593-w

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