Table Of Contents:
Historical Development and Perspectives of the Series v
Preface to Volume 3 vii
Contributors to Volume 3 xvii
Titles of Volumes 1--44 in the Metal Ions in Biological Systems Series xxi
Contents of Volumes in the Metal Ions in Life Sciences Series xxiii

Diversities and Similarities in P450 Systems: An Introduction 1(26)

Mary A. Schuler

Stephen G. Sligar

Oxygenases: Mediators of Biochemical Diversity 2(1)

P450 Superfamily: Diversity at the Sequence Level 3(2)

Diversity of P450 Structures: Folds and Conformations for Functions 5(1)

Diversity in P450 Mechanisms 6(7)

Diversity in Regulation Across the Superfamily 13(3)

Diversity in the Evolution of Common Metabolic Functions 16(2)

Summary and Outlook 18(9)

Acknowledgments 19(1)

Abbreviations 19(1)

References 19(8)

Structural and Functional Mimics of Cytochromes P450 27(30)

Wolf-D. Woggon

Introduction 27(4)

Iron Porphyrins Carrying a Thiolate or Modified Thiolate Ligand 31(9)

Structurally Remote P450 Mimics 40(12)

Concluding Remarks 52(5)

Acknowledgments 52(1)

Abbreviations 53(1)

References 53(4)

Structures of P450 Proteins and Their Molecular Phylogeny 57(40)

Thomas L. Poulos

Yergalem T. Meharenna

Introduction 58(1)

P450 Evolution 59(1)

P450 Families and Subfamilies 60(2)

P450 Structures 62(19)

Variation in P450 Function and Fold 81(5)

Archaeon P450s 86(4)

Summary and Conclusions 90(7)

Acknowledgments 91(1)

Abbreviations 91(1)

References 91(6)

Aquatic P450 Species 97(30)

Mark J. Snyder

Introduction. `P450s Under the Surface' 98(2)

Diversity of Aquatic Species 100(1)

P450 Activities in Aquatic Invertebrates 101(7)

Aquatic P450 Gene Families Identified 108(8)

How Can We Use Information About P450s in Aquatic Species? 116(4)

Conclusions and Outlook 120(7)

Acknowledgments 121(1)

Abbreviations 121(1)

References 122(5)

The Electrochemistry of Cytochrome P450 127(30)

Alan M. Bond

Barry D. Fleming

Lisandra L. Martin

Introduction 127(4)

Redox Titration (Potentiometric Equilibrium) Measurements 131(8)

Voltammetric (Dynamic) Measurements 139(11)

Conclusions 150(7)

Acknowledgments 151(1)

Abbreviations 151(1)

References 152(5)

P450 Electron Transfer Reactions 157(30)

Andrew K. Udit

Stephen M. Contakes

Harry B. Gray

Introduction 158(1)

Catalytic Cycles 158(13)

Electron Tunneling Wires 171(9)

Concluding Remarks 180(7)

Acknowledgments 181(1)

Abbreviations 181(1)

References 181(6)

Leakage in Cytochrome P450 Reactions in Relation to Protein Structural Properties 187(48)

Christiane Jung

Introduction 188(3)

Protein Structural Parameters 191(4)

The Reaction Cycle of Cytochrome P450 195(27)

Protein Structural Parameters and Extent of Competitive Reactions 222(3)

Concluding Remarks 225(10)

Acknowledgments 226(1)

Abbreviations 226(1)

References 227(8)

Cytochromes P450
Structural Basis for Binding and Catalysis 235(32)

Konstanze von Konig

Ilme Schlichting

Introduction 236(1)

Ligand Binding: Substrate Recognition and Access to the Distal Pocket 237(2)

Architecture of the Active Site of CYP101 239(3)

The Distal Acid-Alcohol Pair 242(8)

Experimental Characterization of Reaction Intermediates. Radiolysis as a Tool to Study Redox Reactions 250(3)

Crystal Structures of Oxy-Ferrous Complexes 253(5)

Mechanism: Summary, Conclusions, Speculations 258(9)

Acknowledgments 260(1)

Abbreviations 260(1)

References 261(6)

Beyond Heme-Thiolate Interactions: Roles of the Secondary Coordination Sphere in Cytochrome P450 Systems 267(18)

Yi Lu

Thomas D. Pfister

Overview of Cytochrome P450 Active Site Structure 268(1)

Secondary Coordination Sphere on the Proximal Side 269(6)

Secondary Coordination Sphere on the Distal Side 275(5)

Summary and Outlook 280(5)

Acknowledgments 281(1)

Abbreviations 281(1)

References 281(4)

Interactions of Cytochrome P450 with Nitric Oxide and Related Ligands 285(34)

Andrew W. Munro

Kirsty J. McLean

Hazel M. Girvan

Introduction. Interactions of Ligands and Substrates with P450 Enzymes: General Features 286(3)

Nitric Oxide and Its Interactions with P450s 289(11)

Interactions of Imidazoles and Substituted Imidazoles with P450s 300(5)

Other Ligands and Inhibitors of P450 Function 305(5)

Conclusions and Future Prospects 310(9)

Acknowledgments 310(1)

Abbreviations 311(1)

References 311(8)

Cytochrome P450-Catalyzed Hydroxylations and Epoxidations 319(42)

Roshan Perera

Shengxi Jin

Masanori Sono

John H. Dawson

Introduction 320(2)

The Cytochrome P450 Enzymes 322(5)

Three-Dimensional Structures of the Active Sites of Cytochrome P450 Enzymes 327(6)

Role of the Cys Ligand: the Proximal Thiolate `Push' and Distal Proton-Delivery 333(4)

Multiple Mechanisms of P450 Catalysis 337(6)

Multiple Oxidants in P450 Catalysis 343(4)

Two States Theory 347(1)

Influence of Substrate on the Spectral Properties and Reactivity of P450 Intermediates 348(3)

Formation and Reactivity of Transient P450 Oxygen Intermediates 351(1)

Summary and Future Prospective 352(9)

Acknowledgments 353(1)

Abbreviations 353(1)

References 354(7)

Cytochrome P450 and Steroid Hormone Biosynthesis 361(36)

Rita Bernhardt

Michael R. Waterman

Introduction 362(1)

Steroidogenic P450s 363(11)

Steroid Hormone Biosynthesis in the Adrenal Cortex 374(5)

Steroid Hormone Biosynthesis in the Gonads 379(3)

Extraadrenal and Extragonadal Steroidogenesis 382(3)

Outlook for the Future 385(12)

Acknowledgments 386(1)

Abbreviations 387(1)

References 387(10)

Carbon-Carbon Bond Cleavage by P450 Systems 397(40)

James J. De Voss

Max J. Cryle

Introduction 398(1)

Cleavage Between Oxygenated Carbons 398(10)

Cleavage Alpha to Oxygenated Carbons 408(14)

Cleavage Alpha to Carbon Bearing Nitrogen 422(1)

Carbon-Carbon Bond Cleavage Involving Peroxides 423(6)

General Conclusions 429(8)

Acknowledgments 430(1)

Abbreviations 430(1)

References 430(7)

Design and Engineering of Cytochrome P450 Systems 437(40)

Stephen G. Bell

Nicola Hoskins

Christopher J. C. Whitehouse

Luet L. Wong

Introduction 438(6)

Engineering Bacterial Cytochrome P450 Systems 444(18)

Engineering Mammalian Cytochrome P450 Enzymes 462(5)

Engineering Plant P450 Enzymes 467(1)

Conclusions and Outlook 468(9)

Abbreviations 469(1)

References 469(8)

Chemical Defense and Exploitation. Biotransformation of Xenobiotics by Cytochrome P450 Enzymes 477(84)

Elizabeth M. J. Gillam

Dominic J. B. Hunter

Introduction. Chemical Defense 478(3)

P450 Systems Involved in Chemical Defense 481(48)

Common Themes 529(1)

Industrial Applications of P450 Systems for Xenobiotic Decomposition 530(4)

Conclusions and Future Prospects 534(27)

Acknowledgments 535(1)

Abbreviations 535(2)

References 537(24)

Drug Metabolism as Catalyzed by Human Cytochrome P450 Systems 561(30)

F. Peter Guengerich

Introduction 562(1)

Importance of P450 Enzymes in Drug Metabolism 563(2)

Approaches to Predicting P450 Activity in Humans 565(5)

P450s Involved in Drug Metabolism 570(6)

Examples of Major Issues Involving Drug Metabolism by P450 576(6)

Summary 582(9)

Acknowledgments 583(1)

Abbreviations 583(1)

References 584(7)

Cytochrome P450 Enzymes: Observations from the Clinic 591(28)

Peggy L. Carver

Introduction 592(1)

Drug Interactions 593(1)

Drug Metabolism by Cytochrome P450 Enzymes 594(2)

Alterations in P450 Enzymes 596(7)

Active Transport of Drugs 603(1)

Enzyme-Transporter Cooperativity 603(1)

Use of Probes to Quantitate CYP Activity in Humans 604(1)

Prodrugs 604(1)

The Effect of Intravenous Versus Oral Administration on Drug Interactions 605(1)

Additional Factors Affecting Drug Interactions 606(2)

Herbal and Dietary Effects on CYP 608(2)

Interactions with Commonly Used Medications 610(1)

Beneficial Effects of Drug Interactions 611(1)

FDA Regulations Regarding CYP450-Mediated Drug Interactions 612(1)

Clinical Significance of Drug Interactions 613(1)

Summary 614(5)

Acknowledgment 615(1)

Abbreviations 615(1)

References 615(4)
Subject Index 619