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

Description

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