The dynamic field of flavin and flavoprotein biochemistry has seen rapid advancement in recent years. This comprehensive two volume set provides an overview of all aspects of contemporary research in this important class of enzymes. Topics treated include flavoproteins involved in energy generation, signal transduction and electron transfer (including respiration); oxygen activation by flavoproteins; the biology and biochemistry of complex flavoproteins; flavin and flavoprotein photochemistry/photophysics as well as biotechnological applications of flavoproteins. Recent developments in this field include new structures (including those of large membrane-integral electron transfer complexes containing FMN or FAD), elucidation of the role of flavoproteins in cell signalling pathways (including both phototaxis and the circadian cycle) and important new insights into the reaction mechanisms of flavin-containing enzymes. This volume focussing on oxidases, dehydrogenases and related systems is an essential reference for all researchers in biochemistry, chemistry, photochemistry and photophysics working on flavoenzymes.
Author(s): Russ Hille, Susan M. Miller, Bruce Palfey (Eds.)
Publisher: de Gruyter
Year: 2013
Language: English
Pages: xiv+358
Handbook of Flavoproteins, Volume 1: Oxidases, Dehydrogenases and Related Systems......Page 4
Preface......Page 6
Contributing authors......Page 8
Table of contents......Page 10
1.1 Introduction......Page 16
1.2 The paradigm of bicovalent flavoenzymes: Berberine bridge enzyme (BBE) from Eschscholzia californica......Page 22
1.3 The family of BBE-like enzymes in the plant kingdom: how many and what for?......Page 26
1.4 The occurrence of BBE-like enzymes in fungi......Page 35
1.5 BBE-like enzymes in bacteria: oxidative power for the biosynthesis of antibiotics......Page 37
1.8 References......Page 39
2.1 Importance of proline metabolism......Page 46
2.2 Proline utilization A (PutA) proteins......Page 48
2.3.1 Structures of the catalytic domains of PutA......Page 51
2.3.2 Crystal structure of a minimalist PutA......Page 53
2.4 Reaction kinetics of PutA......Page 55
2.4.1 Proline:ubiquinone oxidoreductase activity......Page 56
2.4.2 Substrate channeling......Page 58
2.5.1 DNA binding......Page 60
2.5.2 Membrane association......Page 62
2.6.1 Redox-linked global conformational changes......Page 64
2.6.2 Local structural changes near the flavin......Page 65
2.6.3 Residues important for functional switching......Page 66
2.7 Conclusions and future research directions......Page 67
2.9 References......Page 68
3.1 Introduction......Page 72
3.2.1 Chorismate synthase......Page 73
3.2.2 4-Hydroxybutyryl-CoA dehydratase......Page 75
3.2.4 4’-Phosphopantothenoylcysteine decarboxylase......Page 77
3.2.5 Other examples......Page 80
3.3.1 Type 2 isopentenyl diphosphate isomerase......Page 81
3.3.2 UDP-galactopyranose mutase......Page 83
3.4 Flavoenzymes for which flavin cofactors play uncertain, but probably catalytic roles......Page 84
3.4.2 Carotene cis-trans isomerase......Page 85
3.5 Conclusions......Page 87
3.6 References......Page 88
4.1 Introduction......Page 94
4.2 Enzymes involved in the production of FMN and FAD in different organisms......Page 95
4.3 FMN and FAD metabolism in yeasts and mammals......Page 98
4.4 FMN and FAD metabolism in bacteria depends on a bifunctional enzyme......Page 103
4.5 FMN and FAD metabolism in plants......Page 106
4.6 Conclusions and future research directions......Page 108
4.8 References......Page 110
4.9 Abbreviations......Page 114
5.1 Introduction......Page 116
5.2.1 Mechanism of chemiexcitation......Page 117
5.2.2 Identity of primary excited state and emitter......Page 120
5.2.3 Multiple forms of 4a-hydroperoxy-FMNH intermediate II......Page 121
5.2.4 Aldehyde substrate inhibition......Page 122
5.3 Flavin reductases – general remarks......Page 123
5.3.2.1 Direct FMNH2 transfer......Page 124
5.3.2.2 Two direct transfer mechanisms......Page 125
5.3.3 Reduced flavin transfers in two-component monooxygenases in general......Page 127
5.5 References......Page 128
6.1 Introduction......Page 134
6.2 D-Amino acid oxidase and related enzymes......Page 135
6.3 Monoamine oxidase and related enzymes......Page 139
6.4 Trimethylamine dehydrogenase......Page 146
6.7 References......Page 148
7.1 Introduction......Page 154
7.2 Structural studies of MAO A and MAO B......Page 156
7.4 Catalytic reaction pathway......Page 159
7.5 Mechanism of C-H bond cleavage and flavin reduction......Page 162
7.7 Biological and pharmacological significance of MAO A and MAO B......Page 164
7.9 References......Page 165
8.1 Introduction......Page 170
8.1.2 Choline, glycine betaine and choline-oxidizing enzymes in biotechnology and medicine......Page 171
8.2.1 Three-dimensional structure......Page 174
8.2.2 Biophysical properties......Page 177
8.2.3 Substrate specificity and inhibitors......Page 178
8.2.5 Chemical mechanism for alcohol oxidation......Page 179
8.2.6 Chemical mechanism for aldehyde oxidation......Page 182
8.2.7 Oxygen activation for reaction with reduced flavin......Page 183
8.4 Thiamine oxidase/dehydrogenase......Page 184
8.7 References......Page 185
9.1 Introduction......Page 192
9.2.1 Importance and applications......Page 193
9.2.2 General biochemical and biophysical properties of P2O......Page 194
9.2.3 Structural studies on P2O......Page 195
9.2.4 Substrate recognition......Page 197
9.2.5 Flavin reduction (sugar oxidation) mechanism......Page 198
9.2.6 Catalytic base for sugar oxidation in the P2O reaction......Page 199
9.2.7 Detection of a C4a-hydroperoxyflavin intermediate in the reaction of P2O......Page 200
9.2.8 The mechanism of H2O2 elimination from C4a-hydroperoxyflavin......Page 202
9.3.1 Biochemical properties and application of GO......Page 203
9.3.2 Flavin reduction of GO......Page 204
9.4 Conclusions and future prospects......Page 205
9.5 References......Page 206
10.1 Introduction......Page 210
10.2.1 Lys265 is the oxygen activation site in MSOX......Page 211
10.2.2 Lys259 is the oxygen activation site in MTOX......Page 214
10.2.3 A pair of lysines comprise the oxygen activation site in TSOX......Page 216
10.2.4 Probing the oxygen activation site in MSOX using chloride as an oxygen surrogate......Page 218
10.2.5 Oxygen access to the proposed activation sites in TSOX and MSOX......Page 221
10.3 Common themes and mechanistic diversity......Page 223
10.4 References......Page 224
11.1 Introduction......Page 228
11.2 Overall structure of soluble ACADs......Page 229
11.2.1 Medium chain acyl-CoA dehydrogenase (MCAD)......Page 230
11.2.4 Very Long Chain Acyl-CoA Dehydrogenase (VLCAD)......Page 232
11.2.5 Position of the catalytic base in primary sequence......Page 234
11.3 The basic biochemical mechanism of the α,β-dehydrogenation step......Page 235
11.3.2 The oxidative half-reaction/interactions of ACADs with electron transferflavoprotein (ETF)......Page 238
11.3.3 The inhibition/inactivation of ACADs......Page 240
11.3.4 Deficiencies of ACADs......Page 241
11.4 Biogenesis of mitochondrial FAO proteins......Page 243
11.5 MCAD deficiency......Page 245
11.6 ETF-QO deficiency......Page 247
11.7 VLCAD deficiency......Page 249
11.8 ACAD 9 deficiency......Page 250
11.9 SCAD deficiency......Page 251
11.9.3 Molecular genetics of SCAD deficiency......Page 252
11.9.4 Molecular pathogenesis of SCAD deficiency......Page 253
11.9.5 Cellular pathological aspects of SCAD deficiency......Page 254
11.12 References......Page 255
12.1 Oxidative protein folding......Page 264
12.3 Two flavin-dependent pathways for protein disulfide bond generation in eukaryotes......Page 266
12.3.1 Quiescin-sulfhydryl oxidases: structural aspects......Page 268
12.3.2 Mechanistic studies of QSOX......Page 269
12.3.3 QSOX can catalyze oxidative protein folding......Page 271
12.3.4 Cellular roles of QSOX......Page 272
12.4.1 Erv2p......Page 273
12.4.2 Disulfide bond formation in the mitochondrial intermembrane space......Page 275
12.4.3 Viral ALR proteins......Page 277
12.5 Ero1......Page 278
12.8 References......Page 279
13.1 Introduction......Page 286
13.1.4 Archeal GltS......Page 287
13.2 The GltS-catalyzed reactions......Page 289
13.4 Localization of catalytic subsites and coenzymes......Page 291
13.5 Mid-point potential values of the GltS cofactors and electron transfer pathway between the GltS flavins......Page 293
13.6 Structure of `GltS and FdGltS and the mechanism of control and coordination of the partial activities......Page 296
13.7 Structure of the NADPH -GltS αβ-protomer......Page 304
13.8 Acknowledgments......Page 306
13.9 References......Page 307
14.1 Biological function......Page 312
14.2.1 Purification......Page 313
14.3.1 Crystallization......Page 314
14.3.2 Overall description of the atomic structure......Page 315
14.4 Mechanism......Page 317
14.4.1 Asymmetric behavior of Class 1A DHODH monomers......Page 319
14.4.2 Class 2 DHODHs and the interaction with membranes......Page 320
14.5 Therapeutic potential......Page 322
14.6 References......Page 323
15.1 Introduction......Page 328
15.2 Classification of FNRs......Page 329
15.4 Interaction of FNR with its natural substrates......Page 333
15.6 Activities of ferredoxin-NADP+ reductase......Page 336
15.7.1 Transgenic expression in E. coli......Page 338
15.7.2.3 Purification of FNR......Page 339
15.7.2.5 Determination of dissociation constant for ApoFNR-FAD complexes......Page 340
15.7.3.1 UV-visible spectroscopy of FNR......Page 341
15.7.3.3 CD spectroscopy of FNR......Page 342
15.9 Acknowledgments......Page 343
15.11 References......Page 344
16.1 Organic halides and biological dehalogenation......Page 352
16.1.1 Strategies for dehalogenation......Page 353
16.2 Flavin-dependent dehalogenation......Page 355
16.2.2 Hydrolytic dehalogenation catalyzed by flavoproteins......Page 356
16.2.3 Reductive dehalogenation catalyzed by flavoproteins......Page 358
16.3 Conclusions......Page 361
16.4 References......Page 362
Index......Page 366
