Peroxiredoxin 1 (Prx1) is a dual-function enzyme by possessing Cys-independent catalase-like activity

• Published in: Biochemical journal Vol. 474; no. 8; p. 1373
• Main Authors: Sun, Cen-Cen, Dong, Wei-Ren, Shao, Tong, Li, Jiang-Yuan, Zhao, Jing, Nie, Li, Xiang, Li-Xin, Zhu, Guan, Shao, Jian-Zhong
• Format: Journal Article
• Language: English
• Published: England 04.04.2017
• Subjects: Amino Acid Substitution; Animals; Binding Sites; Biocatalysis; Cysteine - chemistry; Fish Proteins - antagonists & inhibitors; Fish Proteins - chemistry; Fish Proteins - genetics; Fish Proteins - metabolism; HEK293 Cells; Humans; Hydrogen Peroxide - metabolism; Models, Molecular; Mutagenesis, Site-Directed; Mutation; p38 Mitogen-Activated Protein Kinases - metabolism; Peroxiredoxins - antagonists & inhibitors; Peroxiredoxins - chemistry; Peroxiredoxins - genetics; Peroxiredoxins - metabolism; Phosphorylation; Protein Conformation; Protein Processing, Post-Translational; Reactive Oxygen Species - metabolism; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - metabolism; Recombinant Proteins - chemistry; Recombinant Proteins - metabolism; RNA Interference; Substrate Specificity; Tetraodontiformes; peroxiredoxin 1 (Prx1); puffer fish; ROS; catalase-like activity
• ISSN: 1470-8728
• DOI: 10.1042/bcj20160851

Peroxiredoxin (Prx) was previously known as a Cys-dependent thioredoxin. However, we unexpectedly observed that Prx1 from the green spotted puffer fish (TnPrx1) was able to reduce H O in a manner independent of Cys peroxidation and reductants. This study aimed to validate a novel function for Prx1, delineate the biochemical features and explore its antioxidant role in cells. We have confirmed that Prx1 from the puffer fish and humans truly possesses a catalase (CAT)-like activity that is independent of Cys residues and reductants, but dependent on iron. We have identified that the GVL motif was essential to the CAT-like activity of Prx1, but not to the Cys-dependent thioredoxin peroxidase (POX) activity, and generated mutants lacking POX and/or CAT-like activities for individual functional validation. We discovered that the TnPrx1 POX and CAT-like activities possessed different kinetic features in the reduction of H O The overexpression of wild-type TnPrx1 and mutants differentially regulated the intracellular levels of reactive oxygen species (ROS) and the phosphorylation of p38 in HEK-293T cells treated with H O Prx1 is a dual-function enzyme by acting as POX and CAT with varied affinities towards ROS. This study extends our knowledge on Prx1 and provides new opportunities to further study the biological roles of this family of antioxidants.