Handbook of Flavoproteins, Volume 1: Oxidases, Dehydrogenases and Related Systems 1

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. 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 The dynamic field of flavin and flavoprotein biochemistry has seen rapid advancement in recent years. Thisfirst book of thetwo volume set provides an overview of all aspects focussing on oxidases, dehydrogenases and related systems. Discussed arerecent developments in this field including those of large membrane-integral electron transfer complexes.It is an essential reference for all researchers in biochemistry, chemistry, photochemistry and photophysics working on flavoenzymes