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Science 300 (5619): 650-653

Copyright © 2003 by the American Association for the Advancement of Science

Peroxiredoxin Evolution and the Regulation of Hydrogen Peroxide Signaling

Zachary A. Wood,1* Leslie B. Poole,2 P. Andrew Karplus1{dagger}

Abstract: Eukaryotic 2-Cys peroxiredoxins (2-Cys Prxs) not only act as antioxidants, but also appear to regulate hydrogen peroxide–mediated signal transduction. We showthat bacterial 2-Cys Prxs are much less sensitive to oxidative inactivation than are eukaryotic 2-Cys Prxs. By identifying two sequence motifs unique to the sensitive 2-Cys Prxs and comparing the crystal structure of a bacterial 2-Cys Prx at 2.2 angstrom resolution with other Prx structures, we define the structural origins of sensitivity. We suggest this adaptation allows 2-Cys Prxs to act as floodgates, keeping resting levels of hydrogen peroxide low, while permitting higher levels during signal transduction.

1 Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97333, USA.
2 Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.

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* Present address: Institute of Molecular Biology, Howard Hughes Medical Institute, University of Oregon, Eugene, OR 97403, USA.

{dagger} To whom correspondence should be addressed. E-mail: karplusp{at}

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Molecular Mechanism of the Reduction of Cysteine Sulfinic Acid of Peroxiredoxin to Cysteine by Mammalian Sulfiredoxin.
W. Jeong, S. J. Park, T.-S. Chang, D.-Y. Lee, and S. G. Rhee (2006)
J. Biol. Chem. 281, 14400-14407
   Abstract »    Full Text »    PDF »
Expression of a Mitochondrial Peroxiredoxin Prevents Programmed Cell Death in Leishmania donovani.
S. Harder, M. Bente, K. Isermann, and I. Bruchhaus (2006)
Eukaryot. Cell 5, 861-870
   Abstract »    Full Text »    PDF »
The antioxidant protein alkylhydroperoxide reductase of Helicobacter pylori switches from a peroxide reductase to a molecular chaperone function.
M.-H. Chuang, M.-S. Wu, W.-L. Lo, J.-T. Lin, C.-H. Wong, and S.-H. Chiou (2006)
PNAS 103, 2552-2557
   Abstract »    Full Text »    PDF »
Bioinformatic analysis of the genomes of the cyanobacteria Synechocystis sp. PCC 6803 and Synechococcus elongatus PCC 7942 for the presence of peroxiredoxins and their transcript regulation under stress.
T. Stork, K.-P. Michel, E. K. Pistorius, and K.-J. Dietz (2005)
J. Exp. Bot. 56, 3193-3206
   Abstract »    Full Text »    PDF »
The Role of Peroxiredoxin II in Radiation-Resistant MCF-7 Breast Cancer Cells.
T. Wang, D. Tamae, T. LeBon, J. E. Shively, Y. Yen, and J. J. Li (2005)
Cancer Res. 65, 10338-10346
   Abstract »    Full Text »    PDF »
Oxidative Stress-dependent Structural and Functional Switching of a Human 2-Cys Peroxiredoxin Isotype II That Enhances HeLa Cell Resistance to H2O2-induced Cell Death.
J. C. Moon, Y.-S. Hah, W. Y. Kim, B. G. Jung, H. H. Jang, J. R. Lee, S. Y. Kim, Y. M. Lee, M. G. Jeon, C. W. Kim, et al. (2005)
J. Biol. Chem. 280, 28775-28784
   Abstract »    Full Text »    PDF »
A cysteine-sulfinic acid in peroxiredoxin regulates H2O2-sensing by the antioxidant Pap1 pathway.
A. P. Vivancos, E. A. Castillo, B. Biteau, C. Nicot, J. Ayte, M. B. Toledano, and E. Hidalgo (2005)
PNAS 102, 8875-8880
   Abstract »    Full Text »    PDF »
Substrate Specificity, Localization, and Essential Role of the Glutathione Peroxidase-type Tryparedoxin Peroxidases in Trypanosoma brucei.
T. Schlecker, A. Schmidt, N. Dirdjaja, F. Voncken, C. Clayton, and R. L. Krauth-Siegel (2005)
J. Biol. Chem. 280, 14385-14394
   Abstract »    Full Text »    PDF »
J. C. Williams, C. Sue, G. S. Banting, H. Yang, D. M. Glerum, W. A. Hendrickson, and E. A. Schon (2005)
J. Biol. Chem. 280, 15202-15211
   Abstract »    Full Text »    PDF »
Hydrogen peroxide generated extracellularly by receptor-ligand interaction facilitates cell signaling.
G. J. DeYulia Jr., J. M. Carcamo, O. Borquez-Ojeda, C. C. Shelton, and D. W. Golde (2005)
PNAS 102, 5044-5049
   Abstract »    Full Text »    PDF »
The Mitochondrial Type II Peroxiredoxin F Is Essential for Redox Homeostasis and Root Growth of Arabidopsis thaliana under Stress.
I. Finkemeier, M. Goodman, P. Lamkemeyer, A. Kandlbinder, L. J. Sweetlove, and K.-J. Dietz (2005)
J. Biol. Chem. 280, 12168-12180
   Abstract »    Full Text »    PDF »
Mitochondria as integrators of information in an early-evolving animal: insights from a triterpenoid metabolite.
N. W Blackstone, M. M Kelly, V. Haridas, and J. U Gutterman (2005)
Proc R Soc B 272, 527-531
   Abstract »    Full Text »    PDF »
Reduction of Cysteine Sulfinic Acid by Sulfiredoxin Is Specific to 2-Cys Peroxiredoxins.
H. A. Woo, W. Jeong, T.-S. Chang, K. J. Park, S. J. Park, J. S. Yang, and S. G. Rhee (2005)
J. Biol. Chem. 280, 3125-3128
   Abstract »    Full Text »    PDF »
Peroxiredoxin-linked Detoxification of Hydroperoxides in Toxoplasma gondii.
S. E. Akerman and S. Muller (2005)
J. Biol. Chem. 280, 564-570
   Abstract »    Full Text »    PDF »

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