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Human peroxiredoxin 5 is a peroxynitrite reductase.
Marlène Dubuisson1, Delphine Vander Stricht, André Clippe
1Laboratory of Cell Biology, Institut des Sciences de la Vie, Université catholique de Louvain, 1348 Louvain-la-Neuve, Belgium.
FEBS Letters
|July 29, 2004
Summary
Human peroxiredoxin 5, a key antioxidant enzyme, effectively reduces harmful peroxynitrite. This discovery highlights its role in cellular defense against oxidative stress, particularly via its Cys47 residue.
Area of Science:
- Biochemistry
- Molecular Biology
- Cellular Biology
Background:
- Peroxiredoxins are essential peroxidase enzymes found in all organisms.
- Human peroxiredoxin 5 (Prx5) is the most recently identified mammalian member.
- Prx5 previously demonstrated peroxide reduction using thioredoxin.
Purpose of the Study:
- To investigate the potential of human peroxiredoxin 5 to reduce peroxynitrite.
- To identify the specific cysteine residue responsible for peroxynitrite reduction.
- To quantify the reaction rate of human peroxiredoxin 5 with peroxynitrite.
Main Methods:
- Site-directed mutagenesis of cysteine residues in human peroxiredoxin 5.
- Biochemical assays to assess peroxynitrite reductase activity.
- Pulse radiolysis technique to determine reaction kinetics.
Main Results:
- Human peroxiredoxin 5 exhibits significant peroxynitrite reductase activity.
- Mutational analysis implicates the N-terminal Cys47 in the nucleophilic attack on peroxynitrite.
- Pulse radiolysis revealed a high rate constant of (7+/-3)x10^7 M(-1)s(-1) for peroxynitrite reduction.
Conclusions:
- Human peroxiredoxin 5 functions as a potent peroxynitrite reductase.
- Cys47 is crucial for the catalytic mechanism of peroxynitrite detoxification by Prx5.
- This finding expands the known antioxidant functions of peroxiredoxins in mammals.