Oxidases, Dehydrogenases and Related Systems (eBook)

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Russ Hille, University of California, Riverside, CA, USA; Susan Miller, University of California, San Francisco, CA, USA; Bruce Palfey, University of Michigan, Ann Arbor, MI, USA.

Preface 5
1 Berberine bridge enzyme and the family of bicovalent flavoenzymes 15
1.1 Introduction 15
1.2 The paradigm of bicovalent flavoenzymes: Berberine bridge enzyme (BBE) from Eschscholzia californica 21
1.3 The family of BBE-like enzymes in the plant kingdom: how many and what for? 25
1.4 The occurrence of BBE-like enzymes in fungi 34
1.5 BBE-like enzymes in bacteria: oxidative power for the biosynthesis of antibiotics 36
1.6 Conclusions 38
1.7 Acknowledgments 38
1.8 References 38
2 PutA and proline metabolism 45
2.1 Importance of proline metabolism 45
2.2 Proline utilization A (PutA) proteins 47
2.3 Three-dimensional structures of PutA and PutA domains 50
2.3.1 Structures of the catalytic domains of PutA 50
2.3.2 Crystal structure of a minimalist PutA 52
2.3.3 Solution structure of a trifunctional PutA and the role of the CTD 54
2.4 Reaction kinetics of PutA 54
2.4.1 Proline:ubiquinone oxidoreductase activity 55
2.4.2 Substrate channeling 57
2.5 DNA and membrane binding of trifunctional PutA 59
2.5.1 DNA binding 59
2.5.2 Membrane association 61
2.6 PutA functional switching 63
2.6.1 Redox-linked global conformational changes 63
2.6.2 Local structural changes near the flavin 64
2.6.3 Residues important for functional switching 65
2.7 Conclusions and future research directions 66
2.8 Acknowledgements 67
2.9 References 67
3 Flavoenzymes involved in non-redox reactions 71
3.1 Introduction 71
3.2 Flavoenzymes for which flavin cofactors likely play redox-based catalytic roles 72
3.2.1 Chorismate synthase 72
3.2.2 4-Hydroxybutyryl-CoA dehydratase 74
3.2.3 Polyunsaturated fatty acid isomerase 76
3.2.4 4'-Phosphopantothenoylcysteine decarboxylase 76
3.2.5 Other examples 79
3.3 Flavoenzymes for which flavin cofactors likely play non-redox catalytic roles 80
3.3.1 Type 2 isopentenyl diphosphate isomerase 80
3.3.2 UDP-galactopyranose mutase 82
3.4 Flavoenzymes for which flavin cofactors play uncertain, but probably catalytic roles 83
3.4.1 Lycopene cyclase 84
3.4.2 Carotene cis-trans isomerase 84
3.4.3 Fatty acid hydratase 86
3.4.4 2-Haloacrylate hydratase 86
3.5 Conclusions 86
3.6 References 87
4 Enzymes of FMN and FAD Metabolism 93
4.1 Introduction 93
4.2 Enzymes involved in the production of FMN and FAD in different organisms 94
4.3 FMN and FAD metabolism in yeasts and mammals 97
4.4 FMN and FAD metabolism in bacteria depends on a bifunctional enzyme 102
4.5 FMN and FAD metabolism in plants 105
4.6 Conclusions and future research directions 107
4.7 Acknowledgments 109
4.8 References 109
4.9 Abbreviations 113
5 Mechanisms of bacterial luciferase and related flavin reductases 115
5.1 Introduction 115
5.2 Luciferase mechanism overview 116
5.2.1 Mechanism of chemiexcitation 116
5.2.2 Identity of primary excited state and emitter 119
5.2.3 Multiple forms of 4a-hydroperoxy-FMNH intermediate II 120
5.2.4 Aldehyde substrate inhibition 121
5.3 Flavin reductases – general remarks 122
5.3.1 Mechanisms of flavin reductases in single-enzyme reactions 123
5.3.2 Mechanisms of luciferase:flavin reductase coupled reactions 123
5.3.3 Reduced flavin transfers in two-component monooxygenases in general 126
5.4 Acknowledgments 127
5.5 References 127
6 Amine and amino acid oxidases and dehydrogenases 133
6.1 Introduction 133
6.2 D-Amino acid oxidase and related enzymes 134
6.3 Monoamine oxidase and related enzymes 138
6.4 Trimethylamine dehydrogenase 145
6.5 Conclusions 147
6.6 Acknowledgments 147
6.7 References 147
7 Monoamine oxidases A and B: membrane-bound flavoenzymes of medical importance 153
7.1 Introduction 153
7.2 Structural studies of MAO A and MAO B 155
7.3 Flavin cofactor properties 158
7.4 Catalytic reaction pathway 158
7.5 Mechanism of C-H bond cleavage and flavin reduction 161
7.6 Reaction with O2 to form H2O2 163
7.7 Biological and pharmacological significance of MAO A and MAO B 163
7.8 Acknowledgements 164
7.9 References 164
8 Choline oxidase and related systems 169
8.1 Introduction 169
8.1.1 Glucose-methanol-choline enzyme oxidoreductase superfamily 170
8.1.2 Choline, glycine betaine and choline-oxidizing enzymes in biotechnology and medicine 170
8.2 Choline oxidase 173
8.2.1 Three-dimensional structure 173
8.2.2 Biophysical properties 176
8.2.3 Substrate specificity and inhibitors 177
8.2.4 Steady-state kinetic mechanism 178
8.2.5 Chemical mechanism for alcohol oxidation 178
8.2.6 Chemical mechanism for aldehyde oxidation 181
8.2.7 Oxygen activation for reaction with reduced flavin 182
8.3 Choline dehydrogenase 183
8.4 Thiamine oxidase/dehydrogenase 183
8.5 Conclusions 184
8.6 Acknowledgements 184
8.7 References 184
9 Pyranose oxidases 191
9.1 Introduction 191
9.2 Pyranose 2-oxidase (EC 1.13.10) 192
9.2.1 Importance and applications 192
9.2.2 General biochemical and biophysical properties of P2O 193
9.2.3 Structural studies on P2O 194
9.2.4 Substrate recognition 196
9.2.5 Flavin reduction (sugar oxidation) mechanism 197
9.2.6 Catalytic base for sugar oxidation in the P2O reaction 198
9.2.7 Detection of a C4a-hydroperoxyflavin intermediate in the reaction of P2O 199
9.2.8 The mechanism of H2O2 elimination from C4a-hydroperoxyflavin 201
9.3 Glucose 1-oxidase (EC. 1.1.3.4) 202
9.3.1 Biochemical properties and application of GO 202
9.3.2 Flavin reduction of GO 203
9.3.3 Oxidative half-reaction of GO 204
9.4 Conclusions and future prospects 204
9.5 References 205
10 Toward understanding the mechanism of oxygen activation by flavoprotein oxidases 209
10.1 Introduction 209
10.2 Results and discussion 210
10.2.1 Lys265 is the oxygen activation site in MSOX 210
10.2.2 Lys259 is the oxygen activation site in MTOX 213
10.2.3 A pair of lysines comprise the oxygen activation site in TSOX 215
10.2.4 Probing the oxygen activation site in MSOX using chloride as an oxygen surrogate 217
10.2.5 Oxygen access to the proposed activation sites in TSOX and MSOX 220
10.3 Common themes and mechanistic diversity 222
10.4 References 223
11 The acyl CoA dehydrogenases 227
11.1 Introduction 227
11.2 Overall structure of soluble ACADs 228
11.2.1 Medium chain acyl-CoA dehydrogenase (MCAD) 229
11.2.2 Short chain acyl-CoA dehydrogenase (SCAD) 231
11.2.3 Glutaryl-CoA dehydrogenase (GD) 231
11.2.4 Very Long Chain Acyl-CoA Dehydrogenase (VLCAD) 231
11.2.5 Position of the catalytic base in primary sequence 233
11.3 The basic biochemical mechanism of the a,ß-dehydrogenation step 234
11.3.1 Chain length specificity and pH dependence 237
11.3.2 The oxidative half-reaction/interactions of ACADs with electron transfer flavoprotein (ETF) 237
11.3.3 The inhibition/inactivation of ACADs 239
11.3.4 Deficiencies of ACADs 240
11.4 Biogenesis of mitochondrial FAO proteins 242
11.5 MCAD deficiency 244
11.6 ETF-QO deficiency 246
11.7 VLCAD deficiency 248
11.8 ACAD 9 deficiency 249
11.9 SCAD deficiency 250
11.9.1 Clinical aspects of SCAD deficiency 251
11.9.2 Biochemical aspects of SCAD deficiency 251
11.9.3 Molecular genetics of SCAD deficiency 251
11.9.4 Molecular pathogenesis of SCAD deficiency 252
11.9.5 Cellular pathological aspects of SCAD deficiency 253
11.10 Acknowledgements 254
11.11 Abbreviations 254
11.12 References 254
12 Flavoproteins in oxidative protein folding 263
12.1 Oxidative protein folding 263
12.2 Convergent evolution of three classes of FAD-dependent sulfhydryl oxidases 265
12.3 Two flavin-dependent pathways for protein disulfide bond generation in eukaryotes 265
12.3.1 Quiescin-sulfhydryl oxidases: structural aspects 267
12.3.2 Mechanistic studies of QSOX 268
12.3.3 QSOX can catalyze oxidative protein folding 270
12.3.4 Cellular roles of QSOX 271
12.4 Small ERV domain containing enzymes 272
12.4.1 Erv2p 272
12.4.2 Disulfide bond formation in the mitochondrial intermembrane space 274
12.4.3 Viral ALR proteins 276
12.5 Ero1 277
12.6 Conclusions 278
12.7 Acknowledgments 278
12.8 References 278
13 Glutamate synthase 285
13.1 Introduction 285
13.1.1 NADPH-GltS 286
13.1.2 Fd-GltS 286
13.1.3 NADH-GltS 286
13.1.4 Archeal GltS 286
13.2 The GltS-catalyzed reactions 288
13.3 Flavins and iron-sulfur centers of GltS 290
13.4 Localization of catalytic subsites and coenzymes 290
13.5 Mid-point potential values of the GltS cofactors and electron transfer pathway between the GltS flavins 292
13.6 Structure of aGltS and FdGltS and the mechanism of control and coordination of the partial activities 295
13.7 Structure of the NADPH-GltS aß-protomer 303
13.8 Acknowledgments 305
13.9 References 306
14 The dihydroorotate dehydrogenases 311
14.1 Biological function 311
14.2 Protein production, purification and kinetic characterization 312
14.2.1 Purification 312
14.2.2 Activity test 313
14.3 X-ray structures 313
14.3.1 Crystallization 313
14.3.2 Overall description of the atomic structure 314
14.4 Mechanism 316
14.4.1 Asymmetric behavior of Class 1A DHODH monomers 318
14.4.2 Class 2 DHODHs and the interaction with membranes 319
14.5 Therapeutic potential 321
14.6 References 322
15 Ferredoxin-NADP+ reductases 327
15.1 Introduction 327
15.2 Classification of FNRs 328
15.3 Structural features of FNR 332
15.4 Interaction of FNR with its natural substrates 332
15.5 The metabolic roles of FNR 335
15.6 Activities of ferredoxin-NADP+ reductase 335
15.7 Purification procedures 337
15.7.1 Transgenic expression in E. coli 337
15.7.2 Preparation of soluble protein extracts 338
15.7.3 Spectroscopic properties of FNR 340
15.8 Conclusions 342
15.9 Acknowledgments 342
15.10 Abbreviations 343
15.11 References 343
16 Flavoprotein dehalogenases 351
16.1 Organic halides and biological dehalogenation 351
16.1.1 Strategies for dehalogenation 352
16.2 Flavin-dependent dehalogenation 354
16.2.1 Oxidative dehalogenation by flavoproteins 355
16.2.2 Hydrolytic dehalogenation catalyzed by flavoproteins 355
16.2.3 Reductive dehalogenation catalyzed by flavoproteins 357
16.3 Conclusions 360
16.4 References 361
Index 365