Peroxiredoxin Systems (eBook)

Contents 7
List of contributors 9
Preface 13
1 Introduction 15
Leopold Flohé and J. Robin Harris 15
1. From Early Discoveries to the Emergence of An Ubiquitous Protein Family 15
2. Discovery of the Peroxidase Activity of Peroxiredoxins 18
3. Antioxidant Defence 21
4. Peroxide-Linked Redox Signalling 22
5. Possible Membrane-Association 24
6. Structure 25
6.1. Characterization 25
6.2. Transmission Electron Microscopy 26
6.3. X-ray Crystallography 28
7. Medical Perspectives 29
References 31
2. Evolution of the Peroxiredoxins 40
Bernard Knoops, Eléonore Loumaye and Valérie Van Der Eecken 40
1. Introduction 40
2. Classification of Peroxiredoxins 44
3. Peroxiredoxins in Prokaryotes 46
4. Peroxiredoxins in Archaea 47
5. Peroxiredoxins in Eukaryotes 47
5.1. Yeast (saccharomyces cerevisiae) 47
5.2. Protozoa 47
5.3. Plants 48
5.4. Animals 48
Acknowledgments 50
References 50
3. Structural survey of the Peroxiredoxins 54
P. Andrew Karplus and Andrea Hall 54
1. Scope and Purpose 54
2. Introduction 57
3. Universal Features of the Prx Catalytic Cycle 57
4. Summary of Structural Investigations 59
5. Structural Features Common to all Prxs 59
5.1. Overall Structure 59
6. Features Varying Between Prx Subfamilies 64
6.1. Quaternary Structures 64
6.2. Variations in the Presence and Placement of the Resolving Cys 66
Acknowledgements 71
References 71
4. The Catalytic Mechanism of Peroxiredoxins 74
Leslie B. Poole 74
1. Introduction 74
2. Catalysis of the Peroxide Reduction Step 75
2.1. Reaction at the Critical Cysteine Residue 75
2.2. Other Active Site Residues Participating in Catalysis 77
2.3. Substrate Specificity Studies 78
3. Residues Conserved Among Specific Groups of Prxs with Possible Roles in Catalysis 80
4. Steps in Catalysis Beyond Cysteine Sulfenic Acid Formation: Reduction and Overoxidation 82
4.1. Distinctions between 1-Cys and 2-Cys Peroxidatic Mechanisms 82
4.2. Reductive Recycling of Prxs 83
4.3. Oxidative Inactivation of Prxs during Turnover 84
5. Interplay Between Oligomeric State, Catalysis and Inactivation During Turnover in Typical 2-Cys Prxs 86
6. Conclusions 89
Acknowledgements 89
References 89
5. Kinetics of Peroxiredoxins and their Role in the Decomposition of Peroxynitrite 95
Madia Trujillo, Gerardo Ferrer-Sueta, Leonor Thomson, 95
1. Introduction 96
2. General Approaches to Study Peroxiredoxin Kinetics 98
2.1. Steady-state Kinetic Analysis 99
2.2. Pre-steady State Approaches 109
3. The Special Case: Peroxynitrite 112
3.1. Biochemistry of Peroxynitrite 112
3.2. Pre-steady State Kinetics: Determining the Kineticsof Peroxynitrite-mediated Peroxiredoxin Oxidation, DirectInitial Rate and Competition Approaches 113
3.3. Steady State Approach: Peroxynitrite Reductase Activitiesof Peroxiredoxins 117
3.4. Peroxiredoxins Catalytically Detoxify Peroxynitrite Formedfrom Fluxes of NO and O2 117
4. Relevance of Peroxiredoxin-Catalyzed Peroxynitrite Detoxification 119
Acknowledgements 121
References 121
6 The Peroxiredoxin Repair Proteins 126
Thomas J. Jönsson and W. Todd Lowther 126
1. Introduction 126
2. The Hyperoxidation of Peroxiredoxins 127
3. Retroreduction of Typical 2-Cys Peroxiredoxins 128
3.1. Discovery and Initial Characterization of Sulfiredoxin 129
4. Distribution of Prx Repair Enzymes 131
4.1. Prx Oxidation Susceptibility and Repair Correlations 131
4.2. Tissue Distribution 132
4.3. Conservation of Srx 132
5.1. Novel Protein Fold and Nucleiotide-binding Motif 134
6. Catalytic Properties of Srx 139
6.1. Cofactor Requirements and Catalytic Efficiency 139
6.2. Substrate Specificity and Mutational Analysis 139
6.3. Exploring the Reaction Mechanism 141
7. Importance of Srx in Cell Signalling and Defense 143
7.1. Prx-dependent Peroxide Sensing in Schizosaccharomyces pombe 143
7.2. Src and Chloroplast Protection 144
7.3. Srx and Modulation of Prx Chaperone Function 145
7.4. Srx and (De)glutathionylation Phenomena 147
8. Conclusions 148
Acknowledgements 148
References 148
7. Peroxiredoxins in Bacterial Antioxidant Defense 153
James M. Dubbs and Skorn Mongkolsuk 153
1. Introduction 153
2. Bacterial Alkylhydroperoxidase: AhpC 156
2.1. OxyR Mediated Regulation of AhpC 158
2.2. PerR Mediated Regulation of AhpC 165
2.3. HypR Mediated Regulation of AhpC 168
2.4. AhpC Systems of Indeterminate Regulatory Mechanism 169
2.5. Physiological Role of AhpC 173
3. Tpx: Thiol Preoxidase 179
3.1. Tpx Structure and Biochemistry 179
4. Ohr/OsmC Peroxiredoxin Family 183
4.1. Ohr (Organic Hydroperoxide Resistance) Structure and Biochemistry 183
4.2. Osmotically Inducible Protein: OsmC 188
5. Conclusion 192
Acknowledgements 193
References 193
8. The NADH Oxidase-Prx System in Amphibacillus Xylanus 204
Youichi Niimura 204
1. Introduction 204
2.1. Reaction Mechanism of Hydrogen Peroxide Reduction 206
2.3. Supramolecular Organization of the System 208
3. Physiological Role of the NADH Oxidase-Prx System 210
4. Conclusions 212
Acknowledgments 212
References 213
9. Peroxiredoxin Systems in Mycobacteria 215
Timo Jaeger 215
1. Introduction 215
2. Mycobacterial Peroxiredoxins 216
2.1. Alkyl Hydroperoxide Reductase (AhpC) 216
2.2. Thioredoxin Peroxidase (TPx) 218
2.3. Other Peroxiredoxins in Mycobacteria 220
3. Reduction of Thioredoxins 220
4. Potential Impact for Drug Discovery 221
References 222
10. Peroxiredoxin Systems of Protozoal Parasites 226
Marcel Deponte, Stefan Rahlfs and Katja Becker 226
1. Introduction 226
2. Targeting Redox Metabolism in Protozoal Parasites 227
2.1. Complete Lack or Substitution of One or More Componentsof the Redox System 228
2.2. Differences in the Number and/or the Substrate Specificityof Similar Enzymes 228
2.3. Different Properties of Isofunctional Homologous Proteins 229
3. Properties of Plasmodium Peroxiredoxins 229
3.1. Thioredoxin Peroxidase 1 (TPx-1) 230
3.2. Thioredoxin Peroxidase 2 (TPx-2) 231
3.3. Antioxidant Protein (AOP) 232
3.4. 1-Cys Peroxiredoxin (1-Cys-Prx) 232
4. Future Perspectives 234
Acknowledgements 234
References 234
11. The Trypanothione System 237
Luise R. Krauth-Siegel, Marcelo A. Comini and Tanja Schlecker 237
1. Introduction 237
2. The Parasite Specific Dithiol Trypanothione 238
2.1. Occurrence and Biosynthesis of Trypanothione 238
2.2. Trypanothione is more than Twice Glutathione 239
2.3. The Trypanothione/Tryparedoxin Couple in the RedoxMetabolism of Trypanosomatids 240
3. Trypanothione/Tryparedoxin- Dependent 2-Cys-Peroxiredoxins (Tryparedoxin Peroxidases) 241
3.1. On the Diversity of Tryparedoxin Peroxidases in Trypanosomatids 241
3.2. Specificity and Efficiency of the Tryparedoxin Peroxidases 244
3.3. Catalytic Mechanism of the Trypanosomatid 2-Cys-peroxiredoxins 245
3.4. Three-dimensional Structures of Tryparedoxin Peroxidases 247
3.5. The Tryparedoxin Peroxidases are Resistance and MetastasisFactors and are Essential for the Parasites 249
4. Other Trypanothione-Dependent Perox.Idases 250
4.1. Glutathione Peroxidase-type Tryparedoxin Peroxidases 250
4.2. Ascorbate-dependent Peroxidases 251
Acknowledgements 252
References 252
12. Functions of Typical 2-Cys Peroxiredoxins in Yeast 258
Brian A. Morgan and Elizabeth A. Veal 258
1. Introduction 258
2. Typical 2-Cys Prxs and Signal Transduction 259
2.1. Regulation of H2O2-induced Activation of the Yap1 TranscriptionFactor in S. cerevisiae 260
2.2. Regulation of H2O2-induced Gene Expression in S. pombe 261
3. Typical 2-Cys Prx Act as Molecular Chaperones in S. Cerevisiae 265
4. Typical 2-Cys Prx and the Response to Dna Damage 266
5. Functions of Typical 2-Cys Prx in Other Yeasts 266
5.1. Typical 2-Cys Prx in Candida albicans 266
5.2. Typical 2-Cys Prx in Cryptococcus neoformans 267
6. Conclusions and Perspectives 268
Acknowledgements 268
References 268
13 The Dual Function of Plant Peroxiredoxins in Antioxidant Defence and Redox Signaling 271
Karl-Josef Dietz 271
1. Introduction 271
2. The Principle Types of Peroxiredoxins Based on their Biochemical Properties 274
2.1. Plant Prx Classification 274
2.2. The Gene Family of Peroxiredoxins in Plants and Cyanobacteria 275
3. Catalytic Function and Regeneration of Plant Prx 276
3.1. Peroxide Substrates of Peroxiredoxins 276
3.3. Reduction of PrxQ 280
3.4. 1-Cys Prx 281
3.5. PrxII 281
4. Transcript Regulation of Prx-Genes and~Protein~Accumulation 281
4.1. Tissue Specificity of Expression 282
4.2. Transcript Regulation in Mutants and under Oxidative StressDeduced from Array Hybridisations 282
4.3. Transcript Regulation under Abiotic Stresses 283
4.4. Regulation in Response to Pathogen Infection 285
4.5. Effector Studies 286
5. Plant Prx in Photosynthesis 288
5.1. Peroxiredoxins in Cyanobacterial Photosynthesis 288
5.2. Peroxiredoxins in Plant Photosynthesis 288
6. Prx in Plant Development 289
7. Plant Peroxiredoxins in Signaling and Outlook 291
Acknowledgements 293
References 293
14. Mitochondrial Peroxiredoxins 299
Zhenbo Cao, J. Gordon Lindsay and Neil W. Isaacs 299
1. Introduction 299
1.1. Mitochondria 299
1.2. Oxidative Stress 300
2.3. Protein Oxidative Damage 302
2.4. The Role of Oxidative Stress in Disease 303
2.5. Mitochondrial Antioxidant Defence Systems 304
2.6. Mitochondrial Thioredoxin and Thioredoxin Reductase 305
3. Mitochondrial Prxs 307
3.1. PrxIII 307
3.2. PrxV 307
4. Structure and Catalytic Mechanism of Prxiii and Prx V 308
4.1. PrxIII 308
6. Concluding Remarks 313
References 315
15. Peroxiredoxins in the Lung with Emphasis on~Peroxiredoxin VI 320
Bruno Schremmer, Yefim Manevich, Sheldon I. Feinstein and Aron B. Fisher 320
1. Introduction 321
2. Distribution, Development and Regulation of Prx in the Lung 322
2.1. Distribution 322
2.2. Developmental Regulation 324
2.3. Regulation of Expression in the Mature Lung 324
3. The Peroxidase Activity of Prx VI 325
3.1. The Electron Donor for Prx VI 326
3.2. Substrate Specificity of Prx VI 328
3.3. Structural Determinants for Enzymatic Activity 329
4. Antioxidant Function of Prx VI in the Lung 331
4.1. Cellular Models of Altered Prx VI Expression 334
4.2. Animal Models of Altered Prx VI Expression 335
5. Phospholipase A 2 Activity of Prx VI 336
5.1. Overview of Surfactant Physiology 336
5.2. Properties of Prx VI as a Phospholipase A2 336
5.3. Structural Determinants for Phospholipase Activi 337
5.4. Prx VI and Surfactant Phospholipid Metabolism 338
6. Peroxiredoxins in Lung Disease 340
6.1. Acute Lung Injury 340
6.2. Lung Cancer 340
6.3. Mesothelioma 341
6.4. Sarcoidosis 341
7. Conclusions and Speculation 342
Acknowledgements 342
References 342
16. Peroxiredoxins in Gametogenesis and Embryo Development 348
Isabelle Donnay and Bernard Knoops 348
1. Gametes and Gonads 348
1.1. Testis and Sperm 348
1.2. Ovaries and Oocytes 350
2. Embryo 352
2.1. Preimplantation Embryo 352
2.2. Post-implantation Embryo 353
2.3. Placenta 354
2.4. Perinatal Period 354
3. Insects 355
4. Conclusion 355
Acknowledgments 355
References 356
17. Peroxiredoxins in the Central Nervous System 359
Fumiyuki Hattori and Shinzo Oikawa 359
1. Introduction: Oxidative Stress and the Nervous System 359
1.1. Alzheimer’s Disease (AD) 359
1.2. Parkinson’s Disease (PD) 360
1.3. Amyotrophic Lateral Sclerosis (ALS) 360
1.4. Stroke 361
1.5. Excitotoxicity 361
2. Expression of Peroxiredoxin/Thioredoxin Reductase System in the Nervous System 362
2.1. Basal Expression of Prxs in the CNS 362
2.2. Basal Expression of Trxs in the CNS 363
2.3. Basal Expression of Thiredoxin Reductases in the CNS 364
2.4. Prxs Induction and Reduction in the CNS 364
2.5. Altered Expression of Prxs in Neurodegenerative Diseases 364
2.6. Trx Induction in the CNS 365
2.7. Altered Expression of Trx and TrxR in NeurodegenerativeDiseases 368
2.8. Neuroprotective Effects of Transgenic TrxI Expression 370
2.9. PrxI-presenilin-1 Interactions 371
2.10. Prx-mediated Neuroprotection 371
3. Concluding Remarks and Perspectives 372
References 372
18. Stress-Induced Peroxiredoxins 377
Tetsuro Ishii And Toru Yanagawa 377
1. Introduction 377
2. Activation of Prx I Gene Expression 378
2.1. Prx I gene Activation by Stress Agents in Macrophages 378
2.2. Role of the Nrf2 and Keap1 System in the Induction of Prx IExpression by Electrophiles 379
2.3. Effects of Heme on the Expression and Activity of Prx I 380
2.4. Regulation of the Prx I Expression Levels by Serum or TPA 381
2.5. Signaling Pathways Leading to Prx I Gene Expression by Arsenic 381
2.6. Effects of Oxidative Stress on the Expression of Prx I in the Lung 382
2.7. Activation of Prx I gene Expression in Vivo by Dietary BHA 383
3. Stress Induction of Other Prxs 383
3.1. Stress Induction of Prx III 383
3.2. Activation of Prx II Gene Expression by Radiation 384
4. Conclusions 384
Acknowledgments 384
References 384
Index 387
Color Plates 392