Bioinorganic Chemistry

Transcription

1 PRINCIPLES OF Bioinorganic Chemistry Stephen J. Lippard MASSACHUSETTS INSTITUTE OF TECHNOLOGY Jeremy M. Berg JOHNS HOPKINS SCHOOL OF MEDICINE f V University Science Books Mill Valley, California

2 Preface xv CHAPTER 1 Overview of Bioinorganic Chemistry What is Bioinorganic Chemistry? Metal Functions in Metalloproteins a. Dioxygen Transport b. Electron Transfer c. Structural Roles for Metal Ions Metalloenzyme Functions a. Hydrolytic Enzymes b. Two-Electron Redox Enzymes C Multielectron Pair Redox Enzymes d. Rearrangements Communication Roles for Metals in Biology Interactions of Metal Ions and Nucleic Acids Metal-Ion Transport and Storage Metals in Mediane Organization of This Book 18 Study Problems 19 Bibliography 19 CHAPTER 2 Principles of Coordination Chemistry Related to Bioinorganic Research Thermodynamic Aspects a. The Hard-Soft Acid-Base Concept b. The Chelate Effect and the Irving-Williams Series c. pk a Values of Coordinated Ligands d. Tuning of Redox Potentials e. Biopolymer Effects Kinetic Aspects a. Ligand Exchange Rates b. Substitution Reactions c. Electron Transfer Reactions 30 vii

3 Vlll Contents 2.3. Electronic and Geometrie Structures of Metal Ions in Biology Reactions of Coordinated Ligands Model Complexes and the Concept of Spontaneous Self- Assembly -37 Study Problems 40 Bibliography 41 CHAPTER 3 Properties of Biological Molecules Proteins and Their Constituents a. The Naturally Occurring Amino Acids b. Proteins as Ligands 45 3.I.e. Protein Structure d. Higher-Order Structures e. The Manipulation of Proteins by Gene Cloning and Expression f. The Kinetic Analysis of Enzyme Reactions Nucleic Acids and their Constituents a. RNA, DNA, and Their Building Blocks b. RNA Structure c. DNA Structure d. Metal Binding and Nucleic Acid Structure e. Chromosome Structures f. Nucleic-Acid Synthesis in Vitro g. Sulfur Atoms in Nucleic Acids Other Metal-Binding Biomolecules a. Prosthetic Groups b. CoenzymeB C. Bleomycin and Siderophores d. Complex Assemblies 72 Study Problems 73 Bibliography 73 CHAPTER 4 Physical Methods in Bioinorganic Chemistry Purpose of this Chapter A Comment on Time Scales X-ray Methods a. X-ray Diffraction b. X-ray Absorption Spectroscopy (XAS) Magnetic Resonance Methods a. Electron Paramagnetic Resonance (EPR) Spectroscopy b. Nuclear Magnetic Resonance (NMR) Spectroscopy Mössbauer Spectroscopy 91

4 4.6. Electronic and Vibrational Spectroscopy a. Electronic Spectra b. Vibrational Spectroscopy C. Circular Dichroism and Magnetic Circular Dichroism Spectroscopy Magnetic Measurements Reduction Potential Measurements Electron Microprobe Analysis 98 Study Problems 99 Bibliography 100 CHAPTER 5 Choice, Uptake, and Assembly of Metal Containing Units in Biology Bioavailability of Metal Ions Enrichment Strategies and Intracellular Chemistry of Low- Abundance Metals Spontaneous Self-Assembly of Metal Clusters a. Iron-Sulfur Clusters b. Polyiron Oxo Clusters and Biomineralization Specialized Units a. Porphyrins b. Corrins and Hydroporphyrins c. Metal-Nucleotide Complexes d. Molybdenum-Binding Cofactors 132 Study Problems 136 Bibliography 136 CHAPTER 6 Control and Utilization of Metal-Ion Concentration in Cells Beneficial and Toxic Effects of Metal Ions A Beneficial Metal Under Tight Regulation: Iron a. Solubilization, Uptake and Transport b. Metalloregulation of Uptake and Storage An Example of a Toxic Metal: Mercury a. The Enzymes Involved in Mercury Detoxification b. Metalloregulation of the Mercury Detoxification Genes The Generation and Uses of Metal-Ion-Concentration Gradients a. Generation of Ionic Gradients b. Ion Transport by Ion Channels c. The Acetylcholine Receptor d. The Voltage-Gated Sodium Channel e. Synthetic Models for Ion Channels 167

5 X Contents 6.5. Tissue Selectivity in Metal Drug Distribution 168 Study Problems 170 Bibliography 171 CHAPTER 7 Metal Ion Folding and Cross-Linking of Biomolecules Metal-Ion Stabilization of Protein Structure a. Aspartate Transcarbamoylase b. Zinc-Binding Domains in Nucleic-Acid-Binding Proteins I.C. Calcium-Binding Proteins: Transient Structural Stabilization Metal-Ion Stabilization of Nucleic-Acid Structure a. Transfer RNA b. Catalytic RNA Molecules c. Telomeres Protein Binding to Metallated DNA a. Unwinding and Bending of DNA Modified by Platinum Anticancer Drugs b. Recognition and Binding of High-Mobility-Group (Box) Proteins to DNA Containing Cisplatin IntraStrand d(gpg) or d(apg) Cross-Links Metal-Organized Structures as Probes for Conformation a. Metallointercalators b. Conformational Recognition 206 Study Problems 210 Bibliography 210 CHAPTER 8 Binding of Metal Ions and Complexes to Biomolecule-Active Centers Selection and Insertion of Metal Ions for Protein Sites a. Thermodynamic Control b. Kinetic Control C Bioavailability Preservation of Electroneutrality a. Mononuclear Sites b. Polynuclear Sites Metal-Ion and Metal-Complex Binding to Nucleic Acids Biopolymer-Promoted Metal-Ligand Interactions a. Ferrochelatase b. DNA-Promoted Reaction Chemistry 227 Study Problems 229 Bibliography 229

6 CHAPTER 9 Electron-Transf er Proteins Electron Carriers a. Iron-Sulfur Proteins b. Blue Copper Proteins I.e. Cytochromes Long-Distance Electron Transfer Distance and Driving-Force Dependence of Electron Transfer 247 Study Problems 253 Bibliography 254 CHAPTER 10 Substrate Binding and Activation by Nonredox Mechanisms Hydrolytic Enzymes 258 lo.l.a. Carboxypeptidase A and Thermolysin: Structural Studies 259 lo.l.b. Carboxypeptidase A: Metal Substitution and Spectroscopy I.e. Kinetic Studies and the Postulated Enzyme Mechanism 263 lo.l.d. Alkaline Phosphatase A Lyase, Carbonic Anhydrase An Oxidoreductase, Alcohol Dehydrogenase Nucleotide Activation 274 Study Problems 279 Bibliography 279 CHAPTER 11 Atom- and Group-Transfer Chemistry Dioxygen Transport 284 ll.l.a. Hemoglobin and Myoglobin 285 ll.l.b. Hemerythrin I.e. Hemocyanin Oxygen-Atom-Transfer Reactions: Fe a. Cytochrome P b. Methane Monooxygenase C. Catechol and Other Dioxygenases Oxygen-Atom-Transfer Reactions: Mo a. Molybdenum Oxotransferase Enzymes b. Models for Molybdenum Oxotransferases 322

7 11.4. Other Reactions of Dioxygen and Its Byproducts a. Protective Metalloenzymes: The Cu-Zn Superoxide Dismutase b". A Protective Metalloenzyme, Catalase, and Peroxidases C. Dioxygen Radical-Generating Systems Coenzyme B-12 Dependent Reactions a. Historical Perspective b. Enzymatic Reactions and the Catalytic Mechanism C. Thermodynamic Considerations and the Role of the Enzyme 340 Study Problems 344 Bibliography 344 CHAPTER 12 Protein Tuning of Metal Properties to Achieve Specific Functions The Basic Concept Control of Function by Protein Side Chains: Opening Coordination Sites a. Herne Proteins b. Iron-Sulfur Proteins: Aconitase C. Zinc Proteins Control of Function by Ligand Type a. Herne Proteins b. Iron-Sulfur Proteins: Rieske Centers Control of Function by Coordination Geometry: Blue Copper Proteins Control of Function by Indirect Effects a. [Fe 4 S 4 (Cys) 4 ] Centers: Hydrophobicity and Hydrogen- Bonding Effects b. Cytochromes: Electrostatic Potential Substrate Specificity a. Proteases b. Cytochromes P Coupled Processes BL. Electron Transfer Coupling Sulfite Oxidase b. Chemical and Electron-Transfer Coupling: Nitrogenase C. Substrate Binding: Cytochrome P d. Membrane Transport: Photosynthetic Reaction Center 372 Study Problems 376 Bibliography 377

8 CHAPTER 13 The Frontiers of Bioinorganic Chemistry Choice and Uptake of Metal Ions Control and Utilization of Metal-Ion Concentrations Metal Folding and Cross-Linking Binding of Metal Ions to Biomolecules Electron-Transfer Proteins Substrate Binding and Activation Atom- and Group-Transfer Chemistry Protein Tuning of the Active Sites 388 Study Problems 390 Bibliography 390 Index 393