Bioinorganic Chemistry: A Short Course

BIOINORGANIC CHEMISTRY......Page 3
CONTENTS......Page 9
Preface......Page 15
Acknowledgments......Page 21
1.2 Essential Chemical Elements......Page 23
1.3 Metals in Biological Systems: A Survey......Page 25
1.4 Inorganic Chemistry Basics......Page 28
1.5.1 Thermodynamics......Page 30
1.5.2 Kinetics......Page 31
1.6 Electronic and Geometric Structures of Metals in Biological Systems......Page 35
1.7 Bioorganometallic Chemistry......Page 41
1.8 Electron Transfer......Page 44
1.9 Conclusions......Page 48
References......Page 49
2.1 Introduction......Page 51
2.2.1 Amino Acid Building Blocks......Page 52
2.2.2 Protein Structure......Page 55
2.2.3 Protein Sequencing and Proteomics......Page 61
2.2.4 Protein Function, Enzymes, and Enzyme Kinetics......Page 65
2.3.2 DNA and RNA Molecular Structures......Page 69
2.3.3 Transmission of Genetic Information......Page 75
2.3.4 Genetic Mutations and Site-Directed Mutagenesis......Page 78
2.3.5 Genes and Cloning......Page 80
2.3.6 Genomics and the Human Genome......Page 83
2.4 Zinc-Finger Proteins......Page 85
2.4.1 Descriptive Examples......Page 89
2.5 Summary and Conclusions......Page 95
References......Page 96
3.1.1 Analytical Instrument-Based Methods......Page 98
3.1.2 Spectroscopy......Page 99
3.2.1 Theoretical Aspects and Hardware......Page 100
3.2.2 Descriptive Examples......Page 103
3.3.1 Introduction......Page 105
3.3.2 Crystallization and Crystal Habits......Page 106
3.3.3 Theory and Hardware......Page 110
3.3.4 Descriptive Examples......Page 117
3.4.1 Theoretical Aspects......Page 120
3.4.2 Nuclear Screening and the Chemical Shift......Page 123
3.4.3 Spin–Spin Coupling......Page 126
3.4.4 Techniques of Spectral Integration and Spin–Spin Decoupling......Page 128
3.4.5 Nuclear Magnetic Relaxation......Page 129
3.4.6 The Nuclear Overhauser Effect (NOE)......Page 130
3.4.7 Obtaining the NMR Spectrum......Page 132
3.4.8 Two-Dimensional (2D) NMR Spectroscopy......Page 133
3.4.9 Two-Dimensional Correlation Spectroscopy (COSY) and Total Correlation Spectroscopy (TOCSY)......Page 134
3.4.10 Nuclear Overhauser Effect Spectroscopy (NOESY)......Page 137
3.4.11 Multidimensional NMR......Page 138
3.4.12 Descriptive Examples......Page 139
3.5.1 Theory and Determination of g-Values......Page 144
3.5.2 Hyperfine and Superhyperfine Interactions......Page 149
3.5.4 Descriptive Examples......Page 151
3.6.1 Theoretical Aspects......Page 154
3.6.2 Quadrupole Splitting and the Isomer Shift......Page 156
3.6.3 Magnetic Hyperfine Interactions......Page 158
3.6.4 Descriptive Examples......Page 159
3.7.1 Atomic Force Microscopy......Page 161
3.7.2.1 Stopped-Flow Kinetic Methods......Page 165
3.7.2.2 Flash Photolysis......Page 166
3.7.2.3 Time-Resolved Crystallography......Page 168
3.7.3 Mass Spectrometry......Page 170
3.8 Summary and Conclusions......Page 175
References......Page 176
4.2 Computer Hardware......Page 179
4.3.1 Introduction to MM......Page 182
4.3.2 Molecular Modeling, Molecular Mechanics, and Molecular Dynamics......Page 183
4.3.3 Biomolecule Modeling......Page 188
4.3.4 A Molecular Modeling Descriptive Example......Page 189
4.4.2 Ab Initio Methods......Page 192
4.4.3 Density Function Theory......Page 193
4.4.4 Semiempirical Methods......Page 195
4.5 Computer Software for Chemistry......Page 196
4.5.1 Mathematical Software......Page 202
4.6.1 Nomenclature and Visualization Resources......Page 203
4.6.2 Online Societies, Online Literature Searching, and Materials and Equipment Websites......Page 205
References......Page 207
5.1 Introduction......Page 211
5.2.1 Phosphorus as Phosphate......Page 214
5.2.2 Potassium, Sodium, and Chloride Ions......Page 215
5.2.3 Calcium Homeostasis......Page 216
5.3.1 Passive Diffusion......Page 217
5.3.3 Active Transport—Ion Pumps......Page 219
5.4.1 Na(+)/K(+) ATPase: The Sodium Pump......Page 221
5.4.2.1 Introduction......Page 225
5.4.2.2 X-Ray Crystallographic Studies......Page 227
References......Page 257
6.2.1 Introduction......Page 260
6.2.2 Analyzing the Role of the Metal Ion......Page 263
6.2.3 The Group I Intron Ribozyme......Page 266
6.2.4 The Hammerhead Ribozyme......Page 283
6.3.1 Introduction......Page 323
6.3.2.1 Introduction......Page 324
6.3.2.2 Calmodulin Structure by X-Ray and NMR......Page 325
6.3.2.3 Calmodulin Interactions with Drug Molecules......Page 330
6.3.2.4 Calmodulin–Peptide Binding......Page 335
6.3.2.5 Conclusions......Page 348
6.4.2 Calcium P-Type ATPases......Page 349
6.4.2.1 Ca(2+)-ATPase Protein SERCA1a and the Ca(2+)-ATPase Cycle......Page 351
6.5 Conclusions......Page 359
References......Page 360
7.2 Myoglobin and Hemoglobin......Page 365
7.2.1 Myoglobin and Hemoglobin Basics......Page 367
7.2.2 Structure of the Heme Prosthetic Group......Page 369
7.2.3 Behavior of Dioxygen Bound to Metals......Page 370
7.2.4 Structure of the Active Site in Myoglobin and Hemoglobin: Comparison to Model Compounds......Page 371
7.2.5 Some Notes on Model Compounds......Page 374
7.2.6 Iron-Containing Model Compounds......Page 375
7.2.7 Binding of CO to Myoglobin, Hemoglobin, and Model Compounds......Page 378
7.3 Introduction to Cytochromes......Page 381
7.4.1 Introduction......Page 383
7.4.2 Cytochrome P450: Structure and Function......Page 385
7.4.3 Cytochrome P450: Mechanism of Activity......Page 387
7.4.4 Analytical Methods: X-Ray Crystallography......Page 391
7.4.5.2 A Cytochrome P450 Model Compound: Structural......Page 394
7.4.5.3 Cytochrome P450 Model Compounds: Functional......Page 396
7.5.1 Introduction......Page 404
7.5.2 Cytochrome b(6)f Metal Cofactor Specifics......Page 408
7.6.1 Introduction......Page 410
7.6.2 Cytochrome bc(1) Structure......Page 411
7.6.3 Cytochrome bc(1) Metal Cofactor Specifics......Page 413
7.6.4 The Cytochrome bc(1) Q Cycle......Page 417
7.6.5 Cytochrome bc(1) Inhibitors......Page 419
7.7.1 Introduction......Page 430
7.7.2 Mitochondrial Cytochrome c (Yeast)......Page 433
7.7.3 Mitochondrial Cytochrome c (Horse)......Page 438
7.7.4.1 Cytochrome c Folding......Page 444
7.7.4.2 Electron Transfer in Cytochrome c and Its Redox Partners......Page 446
7.7.4.3 Apoptosis......Page 449
7.8.1 Introduction......Page 451
7.8.2 Metal-Binding Sites in Cytochrome c Oxidase......Page 454
7.8.3 Dioxygen Binding, Proton Translocation, and Electron Transport......Page 456
7.8.4 Cytochrome c Oxidase Model Compounds and Associated Analytical Techniques......Page 462
7.8.5 Cytochrome c Oxidase Conclusions......Page 475
7.9.2 Proteins with Iron–Sulfur Clusters......Page 476
7.9.2.1 The Enzyme Aconitase......Page 477
7.9.3 Iron–Oxo Proteins......Page 480
7.9.3.1 Methane Monooxygenases......Page 481
7.10 Conclusions......Page 487
References......Page 488
Index......Page 499