Iron-Containing Enzymes

by De Visser, Samuel P.; Kumar, Devesh

• ISBN13: 9781849731812
• ISBN10: 1849731810
• Format: Hardcover
• Copyright: 2011-08-25
• Publisher: Royal Society of Chemistry

Summary

There are many mononuclear iron containing enzymes in nature that utilize molecular oxygen and transfer one or both oxygen atoms of O2 to substrates. These enzymes catalyze many processes including the biosynthesis of hormones, the metabolism of drugs, DNA and RNA base repair and, the biosynthesis of antibiotics. Therefore, mononuclear iron containing enzymes are important intermediates in bioprocesses and have great potential in the commercial biosynthesis of specific products since they often catalyze reactions regioselectively or stereospecifically. Understanding their mechanism and function is important and will assist in searches for commercial exploitation. In recent years, advances in experimental as well as theoretical methodologies have made it possible to study the mechanism and function of these enzymes and much information on their properties has been gained. This book highlighting recent developments in the field is, therefore, a timely addition to the literature and will interest a broad readership in the fields of biochemistry, inorganic chemistry and computational chemistry. The Editors, leaders in the field of nonheme and heme iron containing monoxygenases, have filled the book with topical review chapters by leaders in the various sub-disciplines.

Table of Contents

Experimental and Computational Studies on the Catalytic Mechanism of Non-heme Iron Dioxygenases	p. 1
Introduction	p. 1
¿-Ketoglutarate Dependent Dioxygenases (¿KDD) and Halogenases (¿KDH)	p. 3
Taurine/¿-Ketoglutarate Dioxygenase (TauD)	p. 4
AlkB Repair Enzymes	p. 10
Prolyl-4-hydroxylase (P4H)	p. 10
¿-Ketoglutarate Dependent Halogenases (¿KDH)	p. 17
Cysteine Dioxygenase (CDO)	p. 21
Isopenicillin N Synthase (IPNS)	p. 27
1-Aminocyclopropane-1-carboxylic Acid Oxidase (ACCO)	p. 30
Rieske Dioxygenases	p. 32
Extradiol and Intradiol Dioxygenases	p. 34
Conclusion	p. 35
References	p. 36
Non-heme Iron-Dependent Dioxygenases: Mechanism and Structure	p. 42
Introduction	p. 42
Dioxygenases Catalysing Oxidative C-C Cleavage Reactions	p. 43
Intradiol Catechol Dioxygenases	p. 43
Extradiol Catechol Dioxygenases	p. 46
Carotenoid Cleavage Dioxygenases	p. 49
Oxidative Cleavage of Aliphatic Substrates	p. 50
Dioxygenases Catalysing Formation of Peroxides: Lipoxygenases	p. 55
Dioxygenases Catalysing Hydroxylation Reactions	p. 57
¿-Ketoglutarate-Dependent Dioxygenases	p. 57
Arene (Rieske) Dioxygenases	p. 59
Conclusion and Summary	p. 62
References	p. 63
Transient Iron Species in the Catalytic Mechanism of the Archetypal ¿-Ketoglutarate-Dependent Dioxygenase, TauD	p. 67
Introduction	p. 67
Structure of the TauD Active Site	p. 68
Metal Binding to TauD Apoprotein	p. 69
Substrate Binding to TauD	p. 70
Characterization of the NO-Bound Quaternary Complex	p. 71
The Fe(IV)-oxo Species	p. 72
Experimental Detection of Fe(IV)-oxo	p. 72
Electronic Configuration of the Fe(IV)-oxo Species	p. 74
Hydrogen Atom Abstraction by Fe(IV)-oxo	p. 76
Thermodynamics of Hydrogen Atom Abstraction by Fe(IV)-oxo	p. 77
Fe(III)-O(H) Species and Oxygen Transfer	p. 80
Conclusions	p. 83
Acknowledgements	p. 84
References	p. 84
Density Functional Theory Studies on Non-heme Iron Enzymes	p. 88
Introduction	p. 88
Reactions Catalysed by Non-heme Iron Enzymes and their Biological Significance	p. 89
Iron Binding Sites	p. 91
Computational Methods	p. 93
Dioxygen Binding and Generation of Peroxo Intermediates	p. 94
O2 Binding with Oxidation of Fe(II)	p. 94
O2 Binding with Oxidation of the Organic Substrate	p. 96
O2 Binding with Oxidation of External Reductants	p. 98
Strategies for O-O Bond Cleavage	p. 98
Heterolytic O-O Bond Cleavage Leading to Fe(IV)=0	p. 99
Homolytic O-O Bond Cleavage Leading to R-O	p. 101
Heterolytic O-O Bond Cleavage in Fe(IV)-OOH	p. 103
Reactions of the High-Valent Intermediates	p. 104
Oxygenation by Fe(IV)=O	p. 104
Oxidation by Fe(IV)=O	p. 107
Reactions of R-O	p. 110
Origins of Chemoselectivity - The Role of Negative Catalysis	p. 112
Conclusions	p. 114
References	p. 114
Theoretical Spectroscopies of Iron-Containing Enzymes and Biomimetics	p. 119
Introduction	p. 119
Mössbauer Spectroscopy	p. 120
Theoretical Prediction of Mössbauer Parameters	p. 121
Examples from the Literature	p. 123
Nuclear Resonance Vibrational Spectroscopy	p. 125
Examples from the Literature	p. 126
Electron Paramagnetic Resonance	p. 127
Theoretical EPR Spectroscopy	p. 127
Examples from the Literature	p. 130
Absorption Spectroscopy	p. 133
Theoretical Prediction of Absorption Spectroscopy	p. 133
Examples from the Literature	p. 134
X-Ray Spectroscopy	p. 136
Theoretical Prediction of Metal and Ligand X-Edge Spectra	p. 137
Examples from the Literature	p. 138
Conclusion	p. 139
References	p. 140
Bioinspired Non-heme Iron Catalysts in C-H and C=C Oxidation Reactions	p. 148
Biological Precedents	p. 148
Oxidative Iron Proteins	p. 149
Cytochrome P450	p. 150
Rieske Dioxygenases	p. 151
Non-heme Iron Complexes as Bioinspired Catalysts	p. 154
Oxidation of Alkanes (C-H Bonds) by Non-heme Iron Complexes	p. 155
Oxidation of Alkenes (C=C Double Bonds) by Non-heme Iron Complexes	p. 175
Reaction Mechanisms in Catalytic C-H and C=C Oxidation Reactions Mediated by Complexes with N-Rich Ligands	p. 187
The Initially Formed FeIII-OOH and its Cleavage Products	p. 187
Olefin Oxidations: Epoxidation and cis-Dihydroxylation	p. 189
Alkane Oxidations	p. 198
Conclusions	p. 201
References	p. 202
Application of Magnetic Circular Dichroism, X-Ray Absorption Spectroscopy and Extended X-Ray Absorption Fine Structure in Determining Geometric and Electronic Structure of Non-heme Iron(IV)-oxo Enzymatic Intermediates and Related Synthetic Models	p. 209
Introduction	p. 209
Magnetic Circular Dichroism (MCD)	p. 212
X-Ray Absorption Spectroscopy and Extended X-Ray Absorption Fine Structure	p. 223
MCD of Iron(IV)-oxo Complexes	p. 226
[FeIV=0(TMC)(NCCH3)]2+	p. 226
Iron(IV)-oxo MCD: Varying Axial and Equatorial Ligands	p. 230
Vibronic Progression in MCD	p. 233
XAS and EXAFS of Iron(rv)-oxo Intermediates and Synthetic Model Complexes	p. 236
Enzymatic Catalytic Cycle Intermediates	p. 236
Model Complexes	p. 245
Parting Thoughts	p. 250
References	p. 251
Structure, Mechanism and Function of Cytochrome P450 Enzymes	p. 255
Introduction	p. 255
Cytochromes P450 - A Brief History	p. 256
Optical and Spectroscopic Features	p. 257
Cytochrome P450 Catalytic Cycle	p. 260
Biological Diversity	p. 263
Cytochrome P450 Redox Partner Systems	p. 264
Cytochrome P450 Structure	p. 267
Physiological Roles of Cytochromes P450	p. 269
Cytochrome P450 Medicine and Biotechnology	p. 272
Conclusions and Future Prospects	p. 275
References	p. 275
Drug Metabolism by Cytochrome P450: A Tale of Multistate Reactivity	p. 281
Introduction	p. 281
Nomenclature of Cytochrome P450 Enzymes	p. 282
Types of Drag Interactions	p. 283
Induction	p. 283
Inhibition	p. 285
Important Isoforms of Human CYP	p. 285
CYP1A2 Isoform	p. 285
CYP2C8, CYP2C9 and CYP2C19 Isoforms	p. 287
CYP2D6 Isoform	p. 287
CYP3A4 Isoform	p. 287
Examples of Generation of Various Metabolites from a Single CYP 450	p. 288
CYP 450 Structure	p. 290
Catalytic Cycle of CYP 450	p. 291
Compound I of CYP 450: The Active Species	p. 292
Axial Ligand Effect of Compound I	p. 295
Reactivity of Compound I	p. 301
Aliphatic C-H Hydroxylation by Compound I of CYP 450	p. 303
Rearrangement Mechanisms of Aliphatic Hydroxylation Reactions	p. 308
C=C Epoxidation by Compound I of CYP 450	p. 312
Sulfoxidation Reaction by Compound I of CYP 450	p. 315
Aromatic Hydroxylation Reaction by Compound I of CYP 450	p. 317
Role of Water Molecule as Biocatalyst	p. 319
Conclusion	p. 321
Acknowledgements	p. 321
References	p. 321
Oxidation of Unnatural Substrates by Engineered Cytochrome P450cam	p. 330
Introduction	p. 330
Binding of the Substrate	p. 331
CYP 450cam Reaction Cycle	p. 334
Rational Design of the Active Site of CYP 450cam	p. 336
Metabolism of Unnatural Substrates by CYP 450cam Variants	p. 338
Binding of Unnatural Substrate, Hydroxylation, and Product Release	p. 339
Small Hydrocarbons	p. 340
Alkyl Benzenes	p. 344
Polycyclic Aromatic Hydrocarbons (PAHs)	p. 344
2-Ethylhexanol	p. 345
Aromatic-Ahphatic Hydrocarbon, Phenylcyclohexane	p. 346
Diphenylmethane	p. 347
ValporicAcid	p. 347
Terpenoids	p. 348
Fused Benzene-Cycloalkane Compounds	p. 352
Nitrogenous Compounds	p. 352
Halogenated Compounds	p. 355
Summary	p. 357
References	p. 358
QM/MM Studies of Cytochrome P450 Systems: Application to Drug Metabolism	p. 366
Introduction	p. 366
CYPs and Drug Metabolism	p. 369
Quantum Mechanical/Molecular Mechanical (QM/MM) Methods	p. 371
QM/MM Studies of CYPs	p. 374
Catalytic Cycle of CYP 101 (CYP 450cam)	p. 374
Hydroxylation of Camphor by CYP 450cam	p. 380
Compound I Reactivity and Selectivity	p. 383
Aromatic Hydroxylation	p. 387
Other QM/MM Studies of CYPs	p. 391
Conclusions	p. 393
References	p. 394
Mechanism and Function of Tryptophan and Indoleamine Dioxygenases	p. 400
Introduction	p. 400
Biological and Physiological Function of Indoleamine Dioxygenase and Tryptophan Dioxygenase	p. 401
Structures of TDO and IDO	p. 404
Comparison of Overall Structure	p. 404
Active Site Environments	p. 406
Turnover and Inhibition	p. 408
Steady State Kinetics	p. 408
Inhibition of TDO and IDO	p. 410
Catalytic Cycle	p. 411
Formation of the Active Ternary Complex	p. 411
Electrochemical Control of Substrate Reactivity	p. 413
Heme Coordination Environment	p. 414
Mechanism of Oxygen Insertion	p. 418
Summary and Conclusions	p. 421
References	p. 422
Subject Index	p. 427
Table of Contents provided by Ingram. All Rights Reserved.