Preface xi
1 Historical Perspective 1
1.1 Biomineralization 1
1.2 Coagulation 4
1.3 Secondary Messengers (Anticipated) 6
1.4 Colloids 6
1.5 Cross-Linking and Cell Surfaces 8
1.6 Secondary Messengers (Updated) 10
1.7 Pumps Channels and Ionophores 12
1.8 Calcium Binding Proteins 1
1.9 Secondary Messengers (Yet Again) 14
1.10 Mitochondria 16
1.11 Pumps Channels and Ionophores 18
1.12 Hormones 23
1.13 Measurement 26
1.14 Biomineralization: Redux 29
2 Physiological Processes Involving Calcium Binding Proteins 33
2.1 Calcium as a Secondary Messenger 34
2.2 Calcium Buffers 41
2.3 Calcium Pumps and Channels 41
2.4 Mitochondria 42
2.5 Eubacteria 43
2.6 Calcium and Extracellular Proteins 45
2.7 Biomineralization 46
2.8 Calcium and Viruses 51
3 Comparison of the Ca 2+ Ion with Other Metal Cations 55
3.1 Calcium Isotopes 55
3.2 Calcium in the Environment 55
3.3 Uses of Calcium 56
3.4 Health Effects of Calcium 57
3.5 Biologically Significant Metals in the Periodic Table 57
3.6 Hydration of Metal Ions 59
3.7 âHardâ and âSoftâ Metal Ions 60
4 Complexes of Calcium and Other Cations with Compounds of Low Molecular Weight 63
4.1 Crystal Structures of Complexes of Calcium with Low Molecular Weight Compounds 63
4.2 Dissociation Constants of Calcium and Analogs with Small Compounds 66
4.3 Solubilities of Calcium and Analogs with Small Compounds 67
5 Stoichiometry Kinetics and Thermodynamics of Calcium Binding 71
5.1 Stoichiometry Affinity and Cooperativity of Binding 71
5.2 Kinetics of Binding 77
5.3 Partition of Free Energy of Binding (ï½G) Among Enthalpy (ï½H) and Entropy (ï½S) 78
6 Experimental Methods Used to Study Calcium Binding to Proteins 83
6.1 Radioactivity 83
6.2 Ion-Selective Electrodes 84
6.3 Calcium Buffers 85
6.4 Dialysis Equilibrium and Flow 86
6.5 Proteolysis 88
6.6 Deuterium Exchange 88
6.7 Isothermal Titration Calorimetry 89
6.8 Differential Scanning Calorimetry 91
6.9 Mass Spectroscopy 92
6.10 Calcium-Specific Dyes and Fluors 94
6.11 Atomic Flame Absorption Spectroscopy 97
6.12 Absorption Spectroscopy 99
6.13 Fluorescence Spectroscopy 102
6.14 Circular Dichroic and Optical Rotatory Dispersion Spectroscopy 105
6.15 Nuclear Magnetic Resonance 107
6.16 Electron Spin Resonance 110
6.17 Surface Plasmon Resonance 111
6.18 Extended X-ray Absorption Spectroscopy 112
6.19 Small Angle X-ray Scattering 113
6.20 Crystallography 113
7 Structure and Evolution of Proteins 117
7.1 Domain 117
7.2 Structure 119
7.3 Evolution 122
8 Protein Complexes with Metals Other than Calcium 127
8.1 Essential Hard Cations 129
8.2 Essential Metals with Several Valence States 152
8.3 Conclusions 187
9 Nonessential Metals 189
9.1 Alkali Metals (Group Ia) 189
9.2 Alkali Earth Metals (Group IIa) 193
9.3 Group IIIa 197
9.4 Group IVa 204
9.5 Group Va 206
9.6 Group VIIa 206
9.7 Group VIII 207
9.8 Group Ib 209
9.9 Mercury (Group IIb) 210
9.10 Group IIIb 211
9.11 Group IVb 215
9.12 Group Vb 217
9.13 Polonium (Group VIb) 219
9.14 Conclusions and Generalizations 219
10 Parvalbumin 221
10.1 Structure 221
10.2 Function 231
11 EF-Hand Proteins 237
11.1 CTER (Calmodulin Troponin C Essential and Regulatory Light Chain) Subfamily 237
11.2 CPR (Calcineurin B p22 Recoverin) Subfamily 266
11.3 S100 Subfamily 278
11.4 Penta-EF-Hand Subfamily 294
11.5 Proteins with Six EF-Hands 300
11.6 Proteins with Eight and 12 EF-Hands 305
11.7 Proteins with Four EF-Hands 306
11.8 Proteins with Two EF-Hands 315
11.9 EF-Hand Proteins in Bacteria and Viruses 323
12 Cytosolic Calcium Binding Proteins Lacking EF-Hands 327
12.1 Annexins 328
12.2 C2-Domain Proteins 334
12.3 Calcium ATPases 350
12.4 Calcium Binding Proteins of the Endoplasmic Reticulum 354
13 Extracellular Calcium Binding Proteins 361
13.1 α-Lactalbumin 362
13.2 Cell Matrix Proteins 371
13.3 Blood-Clotting Proteins 380
13.4 Osteocalcin 383
13.5 Calcium Binding Lectins 385
13.6 Calcium Binding Hydrolytic Enzymes 389
13.7 Miscellaneous 396
14 Interactions of Calcium Binding Proteins with Other Metal Ions 399
14.1 Magnesium 399
14.2 Sodium and Potassium 402
14.3 Zinc 403
14.4 Trace Metals 406
15 Interactions of Calcium Binding Proteins with Other Proteins and with Membranes 411
15.1 Interactions with Other Proteins 411
15.2 Interactions with Membranes 428
16 Genetic Engineering of Calcium Binding Proteins 439
16.1 Problems 440
16.2 Insertion of Reporter Groups 441
16.3 Mutations in Calcium Binding Sites 442
16.4 Mutations Elsewhere Than in Calcium Binding Sites 448
16.5 Generation of Chimeric Proteins 451
16.6 Creation of Calcium Binding Sites in Proteins 453
16.7 Studies of Proteinâ"Protein and Proteinâ"Membrane Interactions 455
References 459
Index 567
