title: Peroxiredoxin 1 (Prx1) is a dual-function enzyme by possessing Cys-independent catalase-like activity.
abstract: Peroxiredoxin (Prx) was previously known as a Cys-dependent thioredoxin. However, we unexpectedly observed that Prx1 from the green spotted puffer fishTetraodon nigroviridis(TnPrx1) was able to reduce H2O2in 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 H2O2The 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 H2O2Prx1 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.
authors.affiliation: College of Life Sciences, Zhejiang University, and Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Hangzhou 310058, China.
authors.forename: Cen-Cen
authors.initials: CC
authors.lastname: Sun
authors.affiliation: College of Life Sciences, Zhejiang University, and Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Hangzhou 310058, China.
authors.forename: Wei-Ren
authors.initials: WR
authors.lastname: Dong
authors.affiliation: College of Life Sciences, Zhejiang University, and Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Hangzhou 310058, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Shao
authors.affiliation: College of Life Sciences, Zhejiang University, and Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Hangzhou 310058, China.
authors.forename: Jiang-Yuan
authors.initials: JY
authors.lastname: Li
authors.affiliation: College of Life Sciences, Zhejiang University, and Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Hangzhou 310058, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: College of Life Sciences, Zhejiang University, and Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Hangzhou 310058, China.
authors.forename: Li
authors.initials: L
authors.lastname: Nie
authors.affiliation: College of Life Sciences, Zhejiang University, and Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Hangzhou 310058, China shaojz@zju.edu.cn gzhu@cvm.tamu.edu xianglx@zju.edu.cn.
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Xiang
authors.affiliation: College of Life Sciences, Zhejiang University, and Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Hangzhou 310058, China shaojz@zju.edu.cn gzhu@cvm.tamu.edu xianglx@zju.edu.cn.|Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, 4467 TAMU, College Station, Texas 77843, U.S.A.
authors.forename: Guan
authors.initials: G
authors.lastname: Zhu
authors.affiliation: College of Life Sciences, Zhejiang University, and Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Hangzhou 310058, China shaojz@zju.edu.cn gzhu@cvm.tamu.edu xianglx@zju.edu.cn.
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Shao
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D055162:Biocatalysis; D003545:Cysteine / Q000737:chemistry; D029941:Fish Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D054464:Peroxiredoxins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D023721:Tetraodontiformes; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D029941:Fish Proteins; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D006861:Hydrogen Peroxide; C515940:PRDX1 protein, human; D054464:Peroxiredoxins; D048051:p38 Mitogen-Activated Protein Kinases; D003545:Cysteine
keywords: ROS; catalase-like activity; peroxiredoxin 1 (Prx1); puffer fish