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Cyclophilin a binds to peroxiredoxins and activates its peroxidase activity

 Sang Pil Lee  ;  Young Sun Hwang  ;  Yong Jun Kim  ;  Ki-Sun Kwon  ;  Hyung Jung Kim  ;  Kanghwa Kim  ;  Ho Zoon Chae 
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.276(32) : 29826-29832, 2001 
Journal Title
Issue Date
Animals ; Antioxidants/pharmacology ; Ascorbic Acid/pharmacology ; Binding Sites ; Blotting, Western ; Catalysis ; Cyclophilin A/pharmacology* ; Cyclosporine/pharmacology ; Cysteine/chemistry ; Dose-Response Relationship, Drug ; Enzyme Activation ; Escherichia coli/metabolism ; Humans ; Lung/metabolism ; Peroxidases/metabolism* ; Peroxiredoxin VI ; Peroxiredoxins ; Protein Binding ; Protein Conformation ; Rats ; Recombinant Proteins/metabolism ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Subcellular Fractions ; Time Factors
Six distinct peroxiredoxin (Prx) proteins (Prx I-VI) from distinct genes have been identified in mammalian tissues. Prxs are members of a group of peroxidases that have conserved reactive cysteine residue(s) in the active site(s). An immediate physiological electron donor for the peroxidase catalysis for five Prx proteins (Prx I-V) has been identified as thioredoxin (Trx), but that for Prx VI (1-Cys Prx) is still unclear. To identify an immediate electron donor and a binding protein for Prx VI, we performed a Prx VI protein overlay assay. A 20-kDa binding protein was identified by the Prx VI protein overlay assay with flow-through fractions from a High-Q column with rat lung crude extracts. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) and MS-Fit, we identified the 20-kDa Prx VI-binding protein as a cyclophilin A (CyP-A). The binding of recombinant human CyP-A (hCyP-A) to Prx VI was confirmed by using the hCyP-A protein overlay assay and Western immunoblot analysis with hCyP-A-specific antibodies. hCyP-A enhanced the antioxidant activity of Prx VI, as well as the other known mammalian Prx isotypes. hCyP-A supported antioxidant activity of Prx II and Prx VI both against thiol (dithiothreitol)-containing metal-catalyzed oxidation (MCO) systems and ascorbate-containing MCO systems. Prx II was reduced by hCyP-A without help from any other reductant, and the reduction was cyclosporin A-independent. These results strongly suggest that CyP-A not only binds to Prx proteins but also supports its peroxidase activity as an immediate electron donor. In addition, Cys(115) and Cys(161) of hCyP-A were found to be involved in the activation and the reduction of Prx.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyung Jung(김형중) ORCID logo https://orcid.org/0000-0003-2498-0683
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