Handbook of Flavoproteins, Volume 2 - Complex Flavoproteins, Dehydrogenases and Physical Methods

Handbook of Flavoproteins, Volume 2:
Complex Flavoproteins, Dehydrogenases
and Physical Methods......Page 4
Preface......Page 6
Contributing authors......Page 8
Table of contents......Page 10
1.1 Introduction......Page 18
1.2.1 Reactions catalyzed......Page 19
1.2.2 Protein structures......Page 20
1.2.3 Detailed mechanism of PHBH......Page 21
1.2.3.1 Reductive half-reaction......Page 23
1.2.3.2 Oxidative half-reaction......Page 26
1.2.3.3 Hydroxylation chemistry......Page 32
1.3.1 Reactions catalyzed and subclasses......Page 33
1.3.1.1 BVMOs......Page 34
1.3.1.2 FMOs......Page 36
1.3.1.3 NMOs......Page 37
1.3.1.4 YUCCAs......Page 38
1.3.2 Structural features......Page 39
1.4 References......Page 40
2.1 Iron, an essential but scarce nutrient......Page 46
2.2.1 Siderophores are important virulence factors......Page 47
2.3 Flavin-dependent N-hydroxylating monooxygenases......Page 50
2.4 Catalytic cycle of NMOs......Page 51
2.4.1 Flavin reduction in NMOs......Page 52
2.5 Three-dimensional structure of NMOs......Page 54
2.5.2 NADPH-binding domain......Page 57
2.5.3 L-Ornithine-binding domain......Page 58
2.7 Mechanism of stabilization of the C4a-hydroperoxyfl avin by NADP+......Page 59
2.9 Unusual NMOs......Page 61
2.10 High-throughput screening assay to identify inhibitors of NMOs......Page 62
2.11 Conclusions......Page 63
2.12 Referen ces......Page 64
3.1 Introduction......Page 68
3.2.1 Amino acid sequence motifs......Page 71
3.2.2 DNA screening......Page 72
3.3.1 Subclass A......Page 73
3.3.2 Subclass B......Page 75
3.3.3 Subclass C......Page 77
3.3.4 Subclass D......Page 78
3.3.6 Subclass F......Page 79
3.4 Conclusions......Page 81
3.5 References......Page 82
4.1 Introduction......Page 90
4.2 Properties of CYPOR flavins......Page 92
4.4 Membrane binding domain (MBD )......Page 95
4.5 FMN domain......Page 96
4.6 Cytochrome P450 binding: role of the FMN domain
and connecting domain......Page 97
4.8 Mechanism of hydride transfer......Page 99
4.9 Interflavin electron transfer......Page 100
4.11 P450 catalysis......Page 102
4.13 CYPOR domain movement and control of electron transfer......Page 104
4.14 Physiological functions of CYPOR and effects of CYPOR deficiency......Page 107
4.15 Human CYPOR deficiency (PORD )......Page 108
4.17 Unanswered questions and future directions......Page 109
4.18 References......Page 110
5.1 Introduction......Page 120
5.2 Overall structures......Page 121
5.3 Reaction mechanism......Page 122
5.4 Electron transfer from the molybdenum center
to other redox-active centers......Page 130
5.5 Reaction of FAD with NAD+ or molecular oxygen......Page 131
5.6 Inhibitors of xanthine oxidoreductase......Page 133
5.7 References......Page 137
6.1 Introduction and scope......Page 142
6.2 Enzyme structure......Page 143
6.3 Kinetics and mechanism......Page 148
6.4 Post-translational regulation......Page 150
6.5 Interconversion of sulfite oxidase and nitrate reductase activities......Page 152
6.6 Conclusions......Page 154
6.7 References......Page 155
7.1 History of Complex II......Page 158
7.2 Overview of Complex II......Page 160
7.3 Structure of Complex II......Page 161
7.4 Catalytic assays......Page 163
7.5 Catalytic mechanism and domain movement......Page 165
7.6 Electron transfer......Page 168
7.7 Quinone-binding site of Complex II......Page 170
7.8 Assembly of the covalent FAD cofactor into Complex II......Page 172
7.10 References......Page 176
8.1 Introduction......Page 182
8.2 Group 1 FDR enzymes: classic dithiol/disulfide oxidoreductases with a single
CXXXXC disulfide redox center......Page 186
8.2.1 Dihydrolipoamide dehydrogenase (LipDH)......Page 191
8.2.2 Glutathione reductase (GR) – two new structural studies on this classic
member of the group......Page 193
8.3 Group 2A FDR enzymes – enzymes of the Group 1 structural fold requiring
an additional C-terminal Cys-based redox center......Page 194
8.3.1 Mercuric ion reductase (MerA)......Page 197
8.3.2 High Mr thioredoxin reductases (TrxR and TGR)......Page 198
8.4 Group 2B FDR enzymes – low Mr thioredoxin reductase (TrxR )
and structurally related enzymes......Page 200
8.5 Group 3 FDR enzymes – enzymes with cysteine sulfenic acid or mixed
Cys-S-S-CoA redox center......Page 205
8.6 Group 4 FDR enzymes – Group 1-fold enzymes catalyzing novel reactions......Page 209
8.7 Group 5 FDR enzymes – enzymes with a si side pair of Cys residues widely
separated in sequence......Page 211
8.8 References......Page 213
9.1 Introduction......Page 220
9.2.1 Overview......Page 221
9.2.2.1 General......Page 223
9.2.2.2 Mechanisms of the pyrimidine half-reactions......Page 224
Class 2 – Ubiquinone......Page 227
Class 1A – Fumarate......Page 228
Class 1B – NAD......Page 229
9.2.3.1 General......Page 230
9.2.4.1 General......Page 231
9.3.1 Overview......Page 232
9.3.2 Flavin-dependent thymidylate synthase......Page 233
9.3.3 Folate/FAD-dependent methyl transferase (TrmFO )......Page 235
9.4 References......Page 238
10.1 Introduction......Page 242
10.2.1 Moments of the charge distribution......Page 244
10.2.2 Experimental techniques for the determination of excited state
electronic structure......Page 245
10.3 Linear dichroism measurements of reduced anionic flavin transition
dipole moments and complimentary calculations......Page 246
10.4.1 Oxidized flavin......Page 247
10.4.2 Excited state structure of OYE and OYE charge transfer complex......Page 249
10.4.3 DNA photolyase and Δμk0......Page 251
10.4.4 Experimental results for the flavin neutral radical......Page 253
10.5.1 Calculations for oxidized flavins......Page 255
10.5.2 Computational results for semiquinone flavin......Page 257
10.5.3 Computational studies on reduced flavins......Page 258
10.6.1 Time-resolved studies of oxidized flavin......Page 260
10.7 Photoinduced electron transfer in flavins......Page 261
10.8 Applications of flavin photochemistry......Page 262
10.10 References......Page 263
11.1 Introduction......Page 272
11.2 Sulfur limitation in bacterial systems......Page 273
11.3 FMN reductase of the alkanesulfonate monooxygenase system......Page 275
11.4.1 Structural properties of the bacterial luciferase family......Page 276
11.4.2 Structural dynamics of alkanesulfonate monooxygenase......Page 278
11.4.3 Active site structure in the bacterial luciferase family......Page 280
11.4.5 Mechanistic properties of alkanesulfonate monooxygenase......Page 282
11.5 Mechanism of flavin transfer......Page 286
11.7 References......Page 288
12.1 Flavoproteins and electron-transfer reactions......Page 294
12.2 Bulk vs. single-molecule methods......Page 295
12.3 Single-molecule techniques for the study of biological systems......Page 296
12.3.1 Atomic force microscopy......Page 297
12.3.2 Optical tweezers......Page 299
12.3.3 AFM based force spectroscopy......Page 301
12.3.3.1 The avidin-biotin complex......Page 303
12.3.3.3 Molecular interactions in transient complexes......Page 304
12.4.1 Fluorescence measurements......Page 305
12.4.2 Force measurements in flavoproteins......Page 307
Acknowledgements......Page 311
12.5 References......Page 312
13.1.1 History of OYE1......Page 316
13.1.2 OYE 1 structure and roles of key residues......Page 318
13.1.2.3 Threonine 37......Page 319
13.1.2.4 Tryptophan 116......Page 321
13.2 Substrate specificity of OYE 1......Page 322
13.2.1 Ketones and aldehydes......Page 323
13.2.2 Esters......Page 329
13.2.3 Nitro alkenes......Page 332
Acknowledgements......Page 334
13.4 References......Page 335
14.1 Introduction......Page 338
14.2 Computation of Esq/hq on the basis of the crystal structures......Page 339
14.3 Calculation of Esq/hq and determination of redox-linked amino acid residues......Page 341
14.4 Influence of the protein backbone conformation on Esq/hq......Page 342
14.5 Influence of the loop region near the flavin binding site on Esq/hq......Page 343
14.6 Influence of the FMN phosphate group on Esq/hq......Page 346
14.8 References......Page 349
15.1 Introduction......Page 352
15.2.1 The physical basis of the Poisson-Boltzmann equation......Page 353
15.2.2 Electrostatic potentials and electrostatic energies......Page 356
15.3.1 Electrostatic docking of flavoproteins......Page 358
15.3.2 Similarity of electrostatic potentials of proteins......Page 359
15.4 Titration behavior of proteins......Page 361
15.4.1 Microstate model......Page 362
15.4.2 DTPA – An illustrative example......Page 363
15.4.3 Theoretical analysis of the protonation of flavoproteins......Page 366
15.5 Recent and upcoming developments......Page 369
15.6 References......Page 371
16.1 Introduction (light reception in plants)......Page 378
16.2 Plant phototropins......Page 380
16.2.1 LOV domain structure......Page 381
16.2.2 LOV photochemistry......Page 382
16.2.3 LOV signal propagation......Page 386
16.3.1 Cryptochrome structure......Page 388
16.3.2 Cryptochrome photochemistry......Page 391
16.3.3 Cryptochrome signal transduction......Page 395
16.4 Outlook......Page 397
16.5 References......Page 398
17.1 Introduction......Page 410
17.2.1 Steady-state spectroscopic properties......Page 411
17.2.2 Oxidized flavins......Page 413
17.2.3 Anionic and neutral radical flavins......Page 415
17.2.4 Anionic and neutral fully-reduced flavins......Page 416
17.3.1 Experiment design, reaction scheme and probing strategy......Page 418
17.3.2 Femtosecond charge separation, frozen active-site configuration
and critical free energies......Page 420
17.3.3 Ultrafast charge recombination, vibrational quantum effect and hot ground-state cooling......Page 421
17.3.4 Photoinduced redox cycle, reaction time scales, and vibrational coupling generality......Page 423
17.4.1.1 Sequential splitting dynamics of the cyclobutane ring......Page 425
17.4.1.2 Electron tunneling pathways and functional role of adenine moiety......Page 427
17.4.2 Dynamics and mechanism of repair of UV-induced (6-4) photoproduct by
(6-4) photolyase......Page 431
17.4.2.1 Ultrafast electron and proton transfer dynamics......Page 433
17.4.2.2 Catalytic repair photocycle......Page 434
17.5.2 Switching of flavin hydrogen bond in BLUF protein......Page 436
17.6 Conclusions......Page 437
17.7 References......Page 438
Index......Page 446