A key metabolic integrator, coenzyme A, modulates the activity of peroxiredoxin 5 via covalent modification
| Autor: | Sangeun Kim, Laura Palmer, Ivan Gout, Mark Skehel, Giacomo Stanzani, Daniel Silva, Oksana Malanchuk, Bess Yi Kun Yu, Sew Peak Chew, Jovana Baković, Sun-Hee Ahn, Valeriy Filonenko, Tae-Hoon Lee, Lujain Aloum, Michael R. Duchen, Mervyn Singer |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Coenzyme A Clinical Biochemistry DNA Mutational Analysis Oxidative phosphorylation Covalent Interaction Article Peroxiredoxin 5 (Prdx5) Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound Coenzyme A (CoA) 0302 clinical medicine Stress Physiological Animals Humans Rats Wistar Molecular Biology Peroxidase chemistry.chemical_classification biology Chemistry Reactive oxygen species (ROS) PRDX5 Cell Biology General Medicine Peroxiredoxins Oxidants Oxidative Stress 030104 developmental biology Enzyme HEK293 Cells Biochemistry Redox regulation 030220 oncology & carcinogenesis biology.protein Peroxiredoxin Protein Processing Post-Translational Cysteine |
| Zdroj: | Molecular and Cellular Biochemistry |
| ISSN: | 1573-4919 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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