Reversible Ligand Binding
John Wiley & Sons Inc (Verlag)
978-1-119-23848-5 (ISBN)
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Reversible Ligand Binding: Theory and Experiment discusses the physical background of protein-ligand interactions—providing a comprehensive view of the various biochemical considerations that govern reversible, as well as irreversible, ligand binding. Special consideration is devoted to enzymology, a field usually treated separately from ligand binding, but actually governed by identical thermodynamic relationships. Attention is given to the design of the experiment, which aids in showing clear evidence of biochemical features that may otherwise escape notice. Classical experiments are reviewed in order to further highlight the importance of the design of the experiment. Overall, the book supplies students with the understanding that is necessary for interpreting ligand binding experiments, formulating plausible reaction schemes, and analyzing the data according to the chosen model(s).
Topics covered include: theory of ligand binding to monomeric proteins; practical considerations and commonly encountered problems; oligomeric proteins with multiple binding sites; ligand binding kinetics; hemoglobin and its ligands; single-substrate enzymes and their inhibitors; two-substrate enzymes and their inhibitors; and rapid kinetic methods for studying enzyme reactions.
Bridges theory of ligand binding and allostery with experiments
Applies historical and physical insight to provide a clear understanding of ligand binding
Written by a renowned author with long-standing research and teaching expertise in the area of ligand binding and allostery
Based on FEBS Advanced Course lectures on the topic
Reversible Ligand Binding: Theory and Experiment is an ideal text reference for students and scientists involved in biophysical chemistry, physical biochemistry, biophysics, molecular biology, protein engineering, drug design, pharmacology, physiology, biotechnology, and bioengineering.
Andrea Bellelli, PhD is a Professor of Biochemistry at the University of Rome Sapienza. He chaired the Department of Biochemical Sciences "A. Rossi Fanelli" and currently chairs the Medicine and Surgery "B" school at the same University. His research focuses on structural and functional properties of oxygen carrying proteins. Jannette Carey, PhD is a Professor of Chemistry at Princeton University and a visiting scientist of the Academy of Sciences of the Czech Republic at Nové Hrady, where she initiated and organizes a biennial FEBS practical and lecture course, Ligand binding theory and practice.
Preface xi
Acknowledgments xiii
Part I Ligand Binding to Single Binding Site Targets 1
1 Theory of Ligand Binding to Monomeric Proteins 3
1.1 Importance of Ligand]Binding Phenomena in Biology 3
1.2 Preliminary Requirements for Ligand]Binding Study 5
1.3 Chemical Equilibrium and the Law of Mass Action 5
1.4 The Hyperbolic and Sigmoidal Representations of the Ligand]Binding Isotherms 7
1.5 The Important Concept of X1/2 11
1.6 Other Representations of the Ligand]Binding Isotherm 11
1.7 Effect of Temperature: Thermodynamic Relationships 14
1.8 Replacement Reactions: Competitive Ligands 17
1.9 Heterotropic Linkage: Non]Competitive Binding of Two Ligands 20
1.10 Allostery and Allosteric Phenomena in Monomeric Proteins 23
1.11 The Special Case of Cys Ligands (and Similar Reactions) 24
1.12 Other Special Cases 27
2 Ligand]Binding Kinetics for Single]Site Proteins 31
2.1 Basic Concepts of Chemical Kinetics: Irreversible Reactions 31
2.2 Reversible Reactions: Equilibrium and Kinetics 35
2.3 More Complex Kinetic Mechanisms 37
2.4 Reactions with Molecularity Higher Than Two 40
2.5 Classical Methods for the Study of Ligand]Binding Kinetics 41
2.6 Photochemical Kinetic Methods 44
2.7 The Kinetics of Replacement Reactions 47
Appendix to Chapter 2: Principles of Data Analysis 51
3 Practical Considerations and Commonly Encountered Problems 53
3.1 Design of the Experiment: The Free Ligand Concentration 53
3.2 The Signal and the Concentration of the Target 56
3.3 Test of the Reversibility of the Reaction 59
3.4 Frequent Abuses of the Concept of X1/2 60
3.5 Two Common Problems: Protein Precipitation and Baseline Shifts 62
3.6 Low]Affinity Ligands 63
3.7 High]Affinity Ligands 65
3.8 Determination of Binding Stoichiometry 67
3.9 Ligands Occupying a Thermodynamic Phase Different from the Protein 69
3.10 Mixtures of Isoforms 71
3.11 Poor or Absent Signal 73
Part II Ligand Binding to Multiple Binding Site Proteins 75
4 Proteins with Multiple Binding Sites 77
4.1 Multiple Binding Sites: Determination of the Binding Stoichiometry 77
4.2 The Binding Polynomial of a Homooligomeric Protein Made Up of Identical Subunits 79
4.3 Intramolecular Heterogeneity 84
4.4 Oligomeric Proteins with Interacting Binding Events: Homotropic Linkage 86
4.5 Cooperativity: Biochemistry and Physiology 91
4.6 Allostery and Symmetry: The Allosteric Model of Cooperativity 94
4.7 Two Alternative Concepts of Cooperativity 100
4.8 Ligand Replacement in Oligomeric Proteins 104
4.9 Heterotropic Linkage in Multimeric Proteins 105
4.10 Heterotropic Linkage and the Allosteric Model 110
Appendix 4.1 Statistical Distribution of the Ligand Among the Binding Sites: Statistical Factors 112
Appendix 4.2 Symmetry of the X̅ Versus Log([X]) Plot: The Concept of Xm 113
5 Ligand]Linked Association and Dissociation 117
5.1 Quaternary Constraint and Quaternary Enhancement 118
5.2 The Reversibly Dissociating Homodimer Devoid of Ligand]Linked Association Equilibria 119
5.3 Ligand]Linked Association]Dissociation in the Non]Cooperative Homodimer 122
5.4 Oligomers That Dissociate Into Monomers Upon Ligand Binding 126
5.5 Monomers That Self]Associate to Homodimers Upon Ligation 129
5.6 Ligand]Linked Association]Dissociation in Cooperative Proteins 130
5.7 One Ligand Per Dimer: Ligand]Binding Sites at Intersubunit Interfaces 133
5.8 Ligand]Linked Association]Dissociation in the Framework of the Allosteric Model 136
5.9 Practical Considerations 137
6 Kinetics of Ligand Binding to Proteins with Multiple Binding Sites 141
6.1 Stepwise Ligand Binding to Homooligomeric Proteins 141
6.2 Ligand Association to Heterooligomeric Proteins 144
6.3 Study of the Time Course of Ligand Dissociation 145
6.4 Practical Problems in the Study of Ligand]Binding Kinetics with Oligomeric Proteins 149
6.5 Advanced Techniques for the Study of Ligation Intermediates 149
6.6 Integration of Equilibrium and Kinetic Data for Cooperative Systems 153
6.7 Ligand]Binding Kinetics in the Framework of the Allosteric Model 154
Appendix 6.1 Kinetic Statistical Factors 159
7 Hemoglobin and its Ligands 161
7.1 The Heme and Its Ligands 162
7.2 Reversible Ligand Binding and Cooperativity 167
7.3 The Structure of Hemoglobin 172
7.4 Ligation]Dependent Structural Changes 175
7.5 Quaternary Constraint 179
7.6 Structural Aspects of Cooperativity: Allostery 180
7.7 Structure and Energy Degeneracy 184
7.8 Kinetics of Ligand Binding 185
7.9 Ligation Intermediates: Measurement and Structure 189
7.10 Ligand]Linked Dissociation Into Dimers 190
7.11 Non]Human Hemoglobins and Human Hemoglobin Mutants 197
Part III Enzymes: A Special Case of Ligand-Binding Proteins 207
8 Single]Substrate Enzymes and their Inhibitors 209
8.1 Enzymes, Substrates, and Inhibitors: A Special Case of Ligand Binding 209
8.2 Importance of Initial Velocity Studies: Zero Order Kinetics 213
8.3 Linearizations of the Michaelis]Menten Hyperbola 214
8.4 Enzymatic Catalysis of Reversible Reactions 215
8.5 The Study of Enzyme Inhibitors Under the Pseudo]Equilibrium Approximation 217
8.6 Inhibitors that Bind to the Same Site as the Substrate (Pure Competitive Inhibitors) 221
8.7 Different Types of Heterotropic (Non]Competitive) Inhibitors 224
8.8 Heterotropic Regulation of Enzyme Activity 229
9 Two]Substrate Enzymes and their Inhibitors 233
9.1 Two Basic Catalytic Mechanisms for Two]Substrate Enzymes 234
9.2 Steady]State Parameters of Two]Substrate Enzymes that Do Not Form a Ternary Complex 235
9.3 Competitive Inhibitors of Two]Substrate Enzymes That Do Not Form a Ternary Complex 239
9.4 Steady]State Parameters of Two]Substrate Enzymes Forming a Ternary Complex 245
9.5 Competitive Inhibitors of Two]Substrate Enzymes Forming a Ternary Complex 248
10 Beyond the Steady State: Rapid Kinetic Methods for Studying Enzyme Reactions 253
10.1 Structural and Catalytic Properties of Copper]Containing Amine Oxidases 253
10.2 Experimentally Accessible Information on Copper]Amine Oxidases 254
10.3 From Kinetic Constants to Steady]State Parameters 256
10.4 The Method of King]Altman to Derive Steady]State Parameters 261
11 Slowly Binding and Irreversible Enzyme Inhibitors 265
11.1 Definitions and Classifications 266
11.2 Test of Reversibility of Binding 267
11.3 Slowly Equilibrating Competitive Inhibitors 271
11.4 Rapidly Binding Irreversible Inhibitors 276
11.5 Slowly Binding Irreversible Inhibitors 278
11.6 Mechanism]Based Inhibitors 282
Index 287
| Erscheinungsdatum | 16.04.2018 |
|---|---|
| Verlagsort | New York |
| Sprache | englisch |
| Maße | 168 x 246 mm |
| Gewicht | 635 g |
| Themenwelt | Naturwissenschaften ► Biologie ► Biochemie |
| Naturwissenschaften ► Chemie ► Organische Chemie | |
| ISBN-10 | 1-119-23848-X / 111923848X |
| ISBN-13 | 978-1-119-23848-5 / 9781119238485 |
| Zustand | Neuware |
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