Iron-containing Enzymes Versatile Catalysts of Hydroxylation Reactions in Nature

Cover......Page 1
Contents......Page 8
1.1 Introduction......Page 16
1.2 α-Ketoglutarate Dependent Dioxygenases (αKDD) and Halogenases (αKDH)......Page 18
1.2.1 Taurine/a-Ketoglutarate Dioxygenase (TauD)......Page 19
1.2.3 Prolyl-4-hydroxylase (P4H)......Page 25
1.2.4 α-Ketoglutarate Dependent Halogenases(αKDH)......Page 32
1.3 Cysteine Dioxygenase (CDO)......Page 36
1.4 Isopenicillin N Synthase (IPNS)......Page 42
1.5 1-Aminocyclopropane-1-carboxylic Acid Oxidase (ACCO)......Page 45
1.6 Rieske Dioxygenases......Page 47
1.7 Extradiol and Intradiol Dioxygenases......Page 49
1.8 Conclusion......Page 50
References......Page 51
2.1 Introduction......Page 57
2.2.1 Intradiol Catechol Dioxygenases......Page 58
2.2.2 Extradiol Catechol Dioxygenases......Page 61
2.2.3 Carotenoid Cleavage Dioxygenases......Page 64
2.2.4 Oxidative Cleavage of Aliphatic Substrates......Page 65
2.3 Dioxygenases Catalysing Formation of Peroxides: Lipoxygenases......Page 70
2.4.1 α-Ketoglutarate-Dependent Dioxygenases......Page 72
2.4.2 Arene (Rieske) Dioxygenases......Page 74
2.5 Conclusion and Summary......Page 77
References......Page 78
3.1 Introduction......Page 82
3.2 Structure of the TauD Active Site......Page 83
3.2.1 Metal Binding to TauD Apoprotein......Page 84
3.2.2 Substrate Binding to TauD......Page 85
3.2.3 Characterization of the NO-Bound Quaternary Complex......Page 86
3.3.1 Experimental Detection of Fe(IV)-oxo......Page 87
3.3.2 Electronic Configuration of the Fe(IV)-oxo Species......Page 89
3.3.3 Hydrogen Atom Abstraction by Fe(IV)-oxo......Page 91
3.3.4 Thermodynamics of Hydrogen Atom Abstraction by Fe(IV)-oxo......Page 92
3.4 Fe(III)-O(H) Species and Oxygen Transfer......Page 95
3.5 Conclusions......Page 98
References......Page 99
4.1 Introduction......Page 103
4.1.1 Reactions Catalysed by Non-heme Iron Enzymes and their Biological Significance......Page 104
4.1.2 Iron Binding Sites......Page 106
4.2 Computational Methods......Page 108
4.3.1 O2 Binding with Oxidation of Fe(II)......Page 109
4.3.2 O2 Binding with Oxidation of the Organic Substrate......Page 111
4.4 Strategies for O–O Bond Cleavage......Page 113
4.4.1 Heterolytic O–O Bond Cleavage Leading to Fe(IV)=O......Page 114
4.4.2 Homolytic O–O Bond Cleavage Leading to R–O......Page 116
4.4.3 Heterolytic O–O Bond Cleavage inFe(III)–OOH......Page 118
4.5.1 Oxygenation by Fe(IV)=O......Page 119
4.5.2 Oxidation by Fe(IV)–O......Page 122
4.5.3 Reactions of R-O......Page 125
4.6 Origins of Chemoselectivity – The Role of Negative Catalysis......Page 127
References......Page 129
5.1 Introduction......Page 134
5.2 Mo¨ ssbauer Spectroscopy......Page 135
5.2.1 Theoretical Prediction of Mo¨ ssbauer Parameters......Page 136
5.2.2 Examples from the Literature......Page 138
5.3 Nuclear Resonance Vibrational Spectroscopy......Page 140
5.3.1 Examples from the Literature......Page 141
5.4.1 Theoretical EPR Spectroscopy......Page 142
5.4.2 Examples from the Literature......Page 145
5.5.1 Theoretical Prediction of Absorption Spectroscopy......Page 148
5.5.2 Examples from the Literature......Page 149
5.6 X-Ray Spectroscopy......Page 151
5.6.1 Theoretical Prediction of Metal and Ligand K-Edge Spectra......Page 152
5.6.2 Examples from the Literature......Page 153
5.7 Conclusion......Page 154
References......Page 155
6.1 Biological Precedents......Page 163
6.1.1 Oxidative Iron Proteins......Page 164
6.1.2 Cytochrome P450......Page 165
6.1.3 Rieske Dioxygenases......Page 166
6.2 Non-heme Iron Complexes as Bioinspired Catalysts......Page 169
6.2.1 Oxidation of Alkanes (C–H Bonds) by Non-heme Iron Complexes......Page 170
6.2.2 Oxidation of Alkenes (C=C Double Bonds) by Non-heme Iron Complexes......Page 190
6.3.1 The Initially Formed FeIII-OOH and its Cleavage Products......Page 202
6.3.2 Olefin Oxidations: Epoxidation and cis-Dihydroxylation......Page 204
6.3.3 Alkane Oxidations......Page 213
6.4 Conclusions......Page 216
References......Page 217
7.1 Introduction......Page 224
7.1.1 Magnetic Circular Dichroism (MCD)......Page 227
7.1.2 X-Ray Absorption Spectroscopy and Extended X-Ray Absorption Fine Structure......Page 238
7.2.1 [FeIV–O(TMC)(NCCH3)]2+......Page 241
7.2.2 Iron(IV)-oxo MCD: Varying Axial andEquatorial Ligands......Page 245
7.2.3 Vibronic Progression in MCD......Page 248
7.3.1 Enzymatic Catalytic Cycle Intermediates......Page 251
7.3.2 Model Complexes......Page 260
7.4 Parting Thoughts......Page 265
References......Page 266
8.1 Introduction......Page 270
8.2 Cytochromes P450 – A Brief History......Page 271
8.3 Optical and Spectroscopic Features......Page 272
8.4 Cytochrome P450 Catalytic Cycle......Page 275
8.5 Biological Diversity......Page 278
8.6 Cytochrome P450 Redox Partner Systems......Page 279
8.7 Cytochrome P450 Structure......Page 282
8.8 Physiological Roles of Cytochromes P450......Page 284
8.9 Cytochrome P450 Medicine and Biotechnology......Page 287
References......Page 290
9.1 Introduction......Page 296
9.2 Nomenclature of Cytochrome P450 Enzymes......Page 297
9.3.1 Induction......Page 298
9.4.1 CYP1A2 Isoform......Page 300
9.4.4 CYP3A4 Isoform......Page 302
9.5 Examples of Generation of Various Metabolites from a Single CYP 450......Page 303
9.6 CYP 450 Structure......Page 305
9.7 Catalytic Cycle of CYP 450......Page 306
9.8 Compound I of CYP 450: The Active Species......Page 307
9.8.1 Axial Ligand Effect of Compound I......Page 310
9.9 Reactivity of Compound I......Page 316
9.10 Aliphatic C–H Hydroxylation by Compound I of CYP 450......Page 318
9.10.1 Rearrangement Mechanisms of Aliphatic Hydroxylation Reactions......Page 323
9.11 C=C Epoxidation by Compound I of CYP 450......Page 327
9.12 Sulfoxidation Reaction by Compound I of CYP 450......Page 330
9.13 Aromatic Hydroxylation Reaction by Compound I of CYP 450......Page 332
9.14 Role of Water Molecule as Biocatalyst......Page 334
References......Page 336
10.1 Introduction......Page 345
10.2 Binding of the Substrate......Page 346
10.3 CYP 450cam Reaction Cycle......Page 349
10.4 Rational Design of the Active Site of CYP 450cam......Page 351
10.5 Metabolism of Unnatural Substrates by CYP 450 cam Variants......Page 353
10.6 Binding of Unnatural Substrate, Hydroxylation, and Product Release......Page 354
10.6.1 Small Hydrocarbons......Page 355
10.6.3 Polycyclic Aromatic Hydrocarbons (PAHs)......Page 359
10.6.4 2-Ethylhexanol......Page 360
10.6.5 Aromatic–Aliphatic Hydrocarbon, Phenylcyclohexane......Page 361
10.6.7 Valporic Acid......Page 362
10.6.8 Terpenoids......Page 363
10.6.10 Nitrogenous Compounds......Page 367
10.6.11 Halogenated Compounds......Page 370
10.7 Summary......Page 372
References......Page 373
11.1 Introduction......Page 381
11.2 CYPs and Drug Metabolism......Page 384
11.3 Quantum Mechanical/Molecular Mechanical(QM/MM) Methods......Page 386
11.4.1 Catalytic Cycle of CYP101 (CYP 450cam)......Page 389
11.4.2 Hydroxylation of Camphor by CYP 450cam......Page 395
11.4.3 Compound I Reactivity and Selectivity......Page 398
11.4.4 Aromatic Hydroxylation......Page 402
11.4.5 Other QM/MM Studies of CYPs......Page 406
References......Page 408
12.1 Introduction......Page 415
12.2 Biological and Physiological Function of Indoleamine Dioxygenase and Tryptophan Dioxygenase......Page 416
12.3.1 Comparison of Overall Structure......Page 419
12.3.2 Active Site Environments......Page 421
12.4.1 Steady State Kinetics......Page 423
12.4.2 Inhibition of TDO and IDO......Page 425
12.5.1 Formation of the Active Ternary Complex......Page 426
12.5.2 Electrochemical Control of Substrate Reactivity......Page 428
12.5.3 Heme Coordination Environment......Page 429
12.5.4 Mechanism of Oxygen Insertion......Page 433
12.6 Summary and Conclusions......Page 436
References......Page 437
Subject Index......Page 442