The Ubiquitous Roles of Cytochrome P450 Proteins

Looking across the tree of life, it is amazing to find cytochrome P450 proteins represented in all life forms. Volume 3, devoted solely to the vital and still expanding research area concerning P450s, offers in 17 stimulating chapters written by 36 internationally recognized experts an authoritative and timely account of this fascinating subject.
The Ubiquitous Roles of Cytochrome P450 Proteins highlights, supported by nearly 2700 references, more than 20 tables and 190 illustrations, the function of these versatile catalysts which act as monooxygenases and insert an oxygen atom from dioxygen into a substrate molecule oxidizing it. P450s are important in the biosynthesis of hormones and signaling molecules as well as in xenobiotic metabolism and detoxification ranging from pharmaceuticals in humans to toxic substances in insects and plants. Mechanistic aspects and the design and engineering of P450 systems for biotechnological applications are also covered. MILS–3 is essential for scientists working in the wide range from bioinorganic chemistry all the way through to medicine including the clinic.

Spis treści:
HISTORICAL DEVELOPMENT AND PERSPECTIVES OF THE SERIES.
PREFACE TO VOLUME 3.
CONTRIBUTORS TO VOLUME 3.
TITLES OF VOLUMES 1–44 IN THE METAL IONS IN BIOLOGICAL SYSTEMS SERIES.
CONTENTS OF VOLUMES IN THE METAL IONS IN LIFE SCIENCES SERIES.
1 DIVERSITIES AND SIMILARITIES IN P450 SYSTEMS: AN INTRODUCTION (Mary A. Schuler and Stephen G. Sligar).
1. Oxygenases: Mediators of Biochemical Diversity.
2. P450 Superfamily: Diversity at the Sequence Level.
3. Diversity of P450 Structures: Folds and Conformations for Functions.
4. Diversity in P450 Mechanisms.
5. Diversity in Regulation Across the Superfamily.
6. Diversity in the Evolution of Common Metabolic Functions.
7. Summary and Outlook.
Acknowledgments.
Abbreviations.
References.
2 STRUCTURAL AND FUNCTIO NAL MIMICS OF CYTOCHROMES P450 (Wolf–D. Woggon).
1. Introduction.
2. Iron Porphyrins Carrying a Thiolate or Modified Thiolate Ligand.
3. Structurally Remote P450 Mimics.
4. Concluding Remarks.
Acknowledgments.
Abbreviations.
References.
3 STRUCTURES OF P450 PROTEINS AND THEIR MOLECULAR PHYLOGENY (Thomas L. Poulos and Yergalem T. Meharenna).
1. Introduction.
2. P450 Evolution.
3. P450 Families and Subfamilies.
4. P450 Structures.
5. Variation in P450 Function and Fold.
6. Archaeon P450s.
7. Summary and Conclusions.
Acknowledgments.
Abbreviations.
References.
4 AQUATIC P450 SPECIES (Mark J. Snyder).
1. Introduction. ′P450s Under the Surface.′
2. Diversity of Aquatic Species.
3. P450 Activities in Aquatic Invertebrates.
4. Aquatic P450 Gene Families Identified.
5. How Can We Use Information About P450s in Aquatic Species?
6. Conclusions and Outlook.
Acknowledgments.
Abbreviations.
References.
5 THE ELECTROCHEMISTRY OF CYTOCHROME P450 (Alan M. Bond, Barry D. Fleming, and Lisandra L. Martin).
1. Introduction.
2. Redox Titration (Potentiometric Equilibrium) Measurements.
3. Voltammetric (Dynamic) Measurements.
4. Conclusions.
Acknowledgments.
Abbreviations.
References.
6 P450 ELECTRON TRANSFER REACTIONS (Andrew K. Udit, Stephen M. Contakes, and Harry B. Gray).
1. Introduction.
2. Catalytic Cycles.
3. Electron Tunneling Wires.
4. Concluding Remarks.
Acknowledgments.
Abbreviations.
References.
7 LEAKAGE IN CYTOCHROME P450 REACTIONS IN RELATION TO PROTEIN STRUCTURAL PROPERTIES (Christiane Jung).
1. Introduction.
2. Protein Structural Parameters.
3. The Reaction Cycle of Cytochrome P450.
4. Protein Structural Parameters and Extent of Competitive Reactions.
5. Concluding Remarks.
Acknowledgments.
Abbreviations.
References.
8 CYTOCHROMES P450 – STRUCTURAL BASIS FOR BINDING AND CATALYSIS (Konstanze von König and Ilme Schlichting).
1. Introduction.
2. Ligand Binding: Substrate Recognition and Access to the Distal Pocket.
3. Architecture of the Active Site of CYP101.
4. The Distal Acid–Alcohol Pair.
5. Experimental Characterization of Reaction Intermediates. Radiolysis as a Tool to Study Redox Reactions.
6. Crystal Structures of Oxy–Ferrous Complexes.
7. Mechanism: Summary, Conclusions, Speculations.
Acknowledgments.
Abbreviations.
References.
9 BEYOND HEME–THIOLATE INTERACTIONS: ROLES OF THE SECONDARY COORDINATION SPHERE IN CYTOCHROME P450 SYSTEMS (Yi Lu and Thomas D. Pfister).
1. Overview of Cytochrome P450 Active Site Structure.
2. Secondary Coordination Sphere on the Proximal Side.
3. Secondary Coordination Sphere on the Distal Side.
4. Summary and Outlook.
Acknowledgments.
Abbreviations.
References.
10 INTERACTIONS OF CYTOCHROME P450 WITH NITRIC OXIDE AND RELATED LIGANDS (Andrew W. Munro, Kirsty J. McLean, and Hazel M. Girvan).
1. Introduction. Interactions of Ligands and Substrates with P450 Enzymes: General Features.
2. Nitric Oxide and Its Interactions with P450S.
3. Interactions of Imidazoles and Substituted Imidazoles with P450S.
4. Other Ligands and Inhibitors of P450 Function.
5. Conclusions and Future Prospects.
Acknowledgments.
Abbreviations.
References.
11 CYTOCHROME P450–CATALYZED HYDROXYLATIONS AND EPOXIDATIONS (Roshan Perera, Shengxi Jin, Masanori Sono, and John H. Dawson).
1. Introduction.
2. The Cytochrome P450 Enzymes.
3. Three–Dimensional Structures of the Active Sites of Cytochrome P450 Enzymes.
4. Role of the Cys Ligand: the Proximal Thiolate ′Push′ and Distal Proton–Delivery.
5. Multiple Mechanisms of P450 Catalysis.
6. Multiple Oxidants in P450 Catalysis.
7. Two States Theory.
8. Influence of Substrate on the Spectral Properties and Reactivity of P450 Intermediates.
9. Formation and Reactivity of Transient P450 Oxygen Intermediates.
10. Summary and Future Prospective.
Acknowledgments.
Abbreviations.
References.
12 CYTOCHROME P450 AND STEROID HORMONE BIOSYNTHESIS (Rita Bernhardt and Michael R. Waterman).
1. Introduction.
2. Steroidogenic P450s.
3. Steroid Hormone Biosynthesis in the Adrenal Cortex.
4. Steroid Hormone Biosynthesis in the Gonads.
5. Extraadrenal and Extragonadal Steroidogenesis.
6. Outlook for the Future.
Acknowledgments.
Abbreviations.
References.
13 CARBON–CARBON BOND CLEAVAGE BY P450 SYSTEMS (James J. De Voss and Max J. Cryle).
1. Introduction.
2. Cleavage Between Oxygenated Carbons.
3. Cleavage Alpha to Oxygenated Carbons.
4. Cleavage Alpha to Carbon Bearing Nitrogen.
5. Carbon–Carbon Bond Cleavage Involving Peroxides.
6. General Conclusions.
Acknowledgments.
Abbreviations.
References.
14 DESIGN AND ENGINEERING OF CYTOCHROME P450 SYSTEMS (Stephen G. Bell, Nicola Hoskins, Christopher J. C. Whitehouse, and Luet L. Wong).
1. Introduction.
2. Engineering Bacterial Cytochrome P450 Systems.
3. Engineering Mammalian Cytochrome P450 Enzymes.
4. Engineering Plant P450 Enzymes.
5. Conclusions and Outlook.
Abbreviations.
References.
15 CHEMICAL DEFENSE AND EXPLOITATION. BIOTRANSFORMATION OF XENOBIOTICS BY CYTOCHROME P450 ENZYMES (Elizabeth M. J. Gillam and Dominic J. B. Hunter).
1. Introduction. Chemical Defense.
2. P450 Systems Involved in Chemical Defense.
3. Common Themes.
4. Industrial Applications of P450 Systems for Xenobiotic Decomposition.
5. Conclusions and Future Prospects.
Acknowledgments.
Abbreviations.
References.
16 DRUG METABOLISM AS CATALYZED BY HUMAN CYTOCHROME P450 SYSTEMS (