Document Detail


Irreversible oxidation of the active-site cysteine of peroxiredoxin to cysteine sulfonic acid for enhanced molecular chaperone activity.
MedLine Citation:
PMID:  18725414     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The thiol (-SH) of the active cysteine residue in peroxiredoxin (Prx) is known to be reversibly hyperoxidized to cysteine sulfinic acid (-SO(2)H), which can be reduced back to thiol by sulfiredoxin/sestrin. However, hyperoxidized Prx of an irreversible nature has not been reported yet. Using an antibody developed against the sulfonylated (-SO(3)H) yeast Prx (Tsa1p) active-site peptide (AFTFVCPTEI), we observed an increase in the immunoblot intensity in proportion to the H(2)O(2) concentrations administered to the yeast cells. We identified two species of hyperoxidized Tsa1p: one can be reduced back (reversible) with sulfiredoxin, and the other cannot (irreversible). Irreversibly hyperoxidized Tsa1p was identified as containing the active-site cysteine sulfonic acid (Tsa1p-SO(3)H) by mass spectrometry. Tsa1p-SO(3)H was not an autoxidation product of Tsa1p-SO(2)H and was maintained in yeast cells even after two doubling cycles. Tsa1p-SO(3)H self-assembled into a ring-shaped multimeric form was shown by electron microscopy. Although the Tsa1p-SO(3)H multimer lost its peroxidase activity, it gained approximately 4-fold higher chaperone activity compared with Tsa1p-SH. In this study, we identify an irreversibly hyperoxidized Prx, Tsa1p-SO(3)H, with enhanced molecular chaperone activity and suggest that Tsa1p-SO(3)H is a marker of cumulative oxidative stress in cells.
Authors:
Jung Chae Lim; Hoon-In Choi; Yu Sun Park; Hyung Wook Nam; Hyun Ae Woo; Ki-Sun Kwon; Yu Sam Kim; Sue Goo Rhee; Kanghwa Kim; Ho Zoon Chae
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-08-25
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  283     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-10-20     Completed Date:  2008-12-11     Revised Date:  2010-09-21    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  28873-80     Citation Subset:  IM    
Affiliation:
Department of Biological Sciences, Chonnam National University, Gwangju 500-757, Korea.
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MeSH Terms
Descriptor/Qualifier:
Catalytic Domain*
Cysteine / analogs & derivatives*,  chemistry*
Electrophoresis, Gel, Two-Dimensional
Gene Expression Regulation, Fungal*
Hydrogen Peroxide / chemistry
Microscopy, Electron
Models, Biological
Molecular Chaperones / chemistry*
Oxidation-Reduction
Oxidative Stress
Oxygen / chemistry*
Peroxidases / chemistry,  physiology*
Peroxiredoxins / chemistry,  genetics*
Saccharomyces cerevisiae / metabolism
Saccharomyces cerevisiae Proteins / chemistry,  physiology*
Chemical
Reg. No./Substance:
0/Molecular Chaperones; 0/Saccharomyces cerevisiae Proteins; 2381-08-0/cysteine sulfinic acid; 52-90-4/Cysteine; 7722-84-1/Hydrogen Peroxide; 7782-44-7/Oxygen; EC 1.11.1.-/Peroxidases; EC 1.11.1.-/Tsa1 protein, S cerevisiae; EC 1.11.1.15/Peroxiredoxins
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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