BOOK
Paramagnetism in Experimental Biomolecular NMR
Claudio Luchinat | Giacomo Parigi | Enrico Ravera
(2018)
Additional Information
Book Details
Abstract
Paramagnetic NMR is a growing technique that represents an increasingly important tool for the investigation of biomolecules. This book presents an update and overview of the paramagnetic NMR phenomena and effects as well as guidelines for practical implementation of state-of-the-art experiments. All experiments are supported by a solid theoretical foundation. Areas mentioned are the development of solid state NMR, the use of paramagnetic tags providing information on the structure and mobility of the investigated systems, and dynamic nuclear polarization to increase sensitivity.
Compiled by experts in the field, this book has international appeal for researchers as well as students interested in magnetic resonance and structural biology who require experimental support and accessible information.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Cover | Cover | ||
| Preface | v | ||
| List of Acronyms | vii | ||
| List of Symbols | xii | ||
| Contents | xvii | ||
| Chapter 1 NMR Consequences of the Nucleus–Electron Spin Interactions | 1 | ||
| 1.1 The Effect of Paramagnetism on NMR Spectra | 1 | ||
| 1.1.1 The Hyperfine Coupling | 2 | ||
| 1.1.2 The Curie Spin | 4 | ||
| 1.1.3 The Magnetic Susceptibility | 8 | ||
| 1.2 The Hyperfine Shift | 9 | ||
| 1.2.1 The Fermi-contact Shift | 11 | ||
| 1.2.2 The Pseudocontact Shift | 13 | ||
| 1.2.3 Simplified Expressions in Limiting Cases | 17 | ||
| 1.2.4 The Effect of Partial Self-orientation | 18 | ||
| 1.3 The Paramagnetic Residual Dipolar Couplings | 20 | ||
| 1.4 The Paramagnetic Relaxation Enhancements | 23 | ||
| 1.4.1 Dipolar Relaxation | 25 | ||
| 1.4.2 Curie Spin Relaxation | 29 | ||
| 1.4.3 Fermi-contact Relaxation | 30 | ||
| 1.5 Paramagnetic Cross Correlation Effects | 31 | ||
| 1.6 First Principles Calculation of Hyperfine Shifts | 33 | ||
| 1.7 Metal Ion Dependence of the Paramagnetic Effects | 34 | ||
| 1.8 The Overhauser Effect in Paramagnetic Systems | 35 | ||
| Acknowledgements | 37 | ||
| References | 37 | ||
| Chapter 2 Intrinsic and Extrinsic Paramagnetic Probes | 42 | ||
| 2.1 Natural Paramagnetic Centers in Biomolecules | 42 | ||
| 2.1.1 Paramagnetic and Diamagnetic Metal Ions in Proteins | 42 | ||
| 2.1.2 The Importance of a Diamagnetic Reference | 44 | ||
| 2.2 Metal Substitution in Diamagnetic Metalloproteins | 45 | ||
| 2.2.1 Examples of Metal Substitution | 45 | ||
| 2.2.2 Paramagnetic Properties of Lanthanoid Ions | 47 | ||
| 2.3 Chemical Methods for Introducing Paramagnetic Centers into Biomolecules | 48 | ||
| 2.3.1 Tags for Paramagnetic Relaxation Enhancements | 48 | ||
| 2.3.2 Tags for Generating Pseudocontact Shifts | 49 | ||
| 2.4 Introducing Paramagnetic Centers in Biomolecules by Genetic Encoding | 73 | ||
| 2.4.1 Metal-binding Unnatural Amino Acids | 73 | ||
| 2.4.2 Fusion with Lanthanoid Binding Peptides | 74 | ||
| 2.4.3 Fusion with Copper(II) and Nickel(II) Binding Peptides | 74 | ||
| 2.4.4 Specific Non-covalent Binding of a Paramagnetic Reporter Protein | 75 | ||
| 2.5 Conclusion and Prospects | 75 | ||
| Acknowledgements | 76 | ||
| References | 76 | ||
| Chapter 3 Structural and Dynamic Characterization of Protein Domains using Paramagnetic Data | 85 | ||
| 3.1 The Utility of Paramagnetic Effects | 85 | ||
| 3.2 Implementation of Restraints from Paramagnetic Relaxation Enhancement | 87 | ||
| 3.3 Implementation of Restraints from Pseudocontact Shifts | 92 | ||
| 3.4 Implementation of Restraints from Field Induced Residual Dipolar Couplings | 96 | ||
| 3.5 Application Involving Both PCSs and RDCs | 100 | ||
| References | 103 | ||
| Chapter 4 Treating Biomacromolecular Conformational Variability | 107 | ||
| 4.1 Introduction | 107 | ||
| 4.2 Experimental Techniques | 108 | ||
| 4.2.1 What Does an Experiment Really Observe? | 108 | ||
| 4.2.2 Pseudocontact Shifts and Residual Dipolar Couplings from Self-alignment | 109 | ||
| 4.2.3 Residual Dipolar Couplings from External Alignment | 112 | ||
| 4.2.4 Relaxation Rates | 112 | ||
| 4.2.5 Small Angle Scattering and Other Techniques | 113 | ||
| 4.2.6 The Information Content of the Different Types of Average Data | 114 | ||
| 4.3 Principles of Ensemble Averaging | 119 | ||
| 4.3.1 Maximum Entropy | 120 | ||
| 4.3.2 Largest Weight | 121 | ||
| 4.3.3 A Comparison of Different Approaches | 123 | ||
| 4.3.4 Some Examples | 125 | ||
| Acknowledgements | 129 | ||
| References | 129 | ||
| Chapter 5 Protein–Protein Interactions | 134 | ||
| 5.1 Introduction | 134 | ||
| 5.2 Protein–Protein Interactions | 135 | ||
| 5.3 The New Toolbox | 136 | ||
| 5.4 Tight Complexes: Breaking Symmetry | 139 | ||
| 5.5 Ground States Structures of Protein Complexes | 141 | ||
| 5.6 Dynamics and Encounter States | 143 | ||
| 5.7 Examples of Applications | 146 | ||
| 5.7.1 Breaking the Symmetry of the STAT Complex | 146 | ||
| 5.7.2 Synaptotagmin-1–SNARE Complex | 146 | ||
| 5.7.3 Cytochrome f and Plastocyanin | 147 | ||
| 5.7.4 Cytochrome f and Cytochrome c6 | 148 | ||
| 5.7.5 Cytochrome c and Adrenodoxin | 150 | ||
| 5.7.6 Cytochrome P450cam and Putidaredoxin | 150 | ||
| 5.7.7 Ferredoxin, Ferredoxin:Thioredoxin Reductase and Thioredoxin | 152 | ||
| 5.7.8 Cytochrome c Peroxidase and Cytochrome c | 153 | ||
| 5.7.9 Enzyme I and the Histidine-containing Phosphocarrier Protein | 154 | ||
| 5.7.10 NS2B–NS3 Protease | 155 | ||
| 5.8 Conclusions and Perspective | 156 | ||
| References | 158 | ||
| Chapter 6 Solid-state NMR of Paramagnetic Proteins | 163 | ||
| 6.1 Introduction | 163 | ||
| 6.2 Paramagnetic Effects and Solid-state NMR | 164 | ||
| 6.2.1 Paramagnetic Relaxation Enhancement (PRE) | 164 | ||
| 6.2.2 The Curie Spin and the Paramagnetic Shift Anisotropy | 165 | ||
| 6.2.3 The Hyperfine Shift | 166 | ||
| 6.3 Magic-angle Spinning | 168 | ||
| 6.3.1 Slow Magic-angle Spinning | 168 | ||
| 6.3.2 Fast Magic-angle Spinning | 170 | ||
| 6.3.3 1H detection | 173 | ||
| 6.4 Paramagnetic Effects as Long-range Structural Restraints | 176 | ||
| 6.4.1 Pseudocontact Shifts | 176 | ||
| 6.4.2 Paramagnetic Relaxation Enhancements | 178 | ||
| 6.5 Breaking into the Blind Sphere | 179 | ||
| 6.5.1 Spin-echoed Acquisitions | 179 | ||
| 6.5.2 Adiabatic Inversion and Refocusing Pulses | 180 | ||
| 6.5.3 Heteronuclear Correlations | 181 | ||
| 6.5.4 Infinite-speed MAS Spectra | 182 | ||
| 6.5.5 A Case Study | 182 | ||
| 6.6 Conclusions | 184 | ||
| References | 184 | ||
| Chapter 7 Relaxometry and Contrast Agents | 189 | ||
| 7.1 Introduction | 189 | ||
| 7.2 Basics of the Paramagnetic Relaxation Enhancement | 192 | ||
| 7.2.1 Structural and Dynamic Determinants of the Observed Relaxivity | 195 | ||
| 7.3 Applications of Paramagnetic Agents in MRI | 200 | ||
| 7.3.1 Dynamic Contrast Enhanced MRI (DCE-MRI) | 202 | ||
| 7.3.2 Molecular Imaging Targeting Reporters | 204 | ||
| 7.3.3 Responsive Paramagnetic Probes | 207 | ||
| 7.4 Conclusions | 213 | ||
| References | 214 | ||
| Chapter 8 Dynamic Nuclear Polarization | 219 | ||
| 8.1 NMR Sensitivity and Spin Polarization | 219 | ||
| 8.1.1 The Zeeman Polarization in Thermal Equilibrium | 219 | ||
| 8.1.2 Sensitivity Enhancement by Paramagnetic Species | 221 | ||
| 8.1.3 Hyperpolarization Methods | 221 | ||
| 8.2 DNP Mechanisms | 222 | ||
| 8.2.1 Overview | 222 | ||
| 8.2.2 The Solid Effect | 223 | ||
| 8.2.3 The Cross Effect | 227 | ||
| 8.2.4 The Overhauser Effect | 231 | ||
| 8.3 Polarizing Agents and DNP Profiles | 234 | ||
| 8.3.1 Requirements of Polarizing Agents | 234 | ||
| 8.3.2 DNP Field or Frequency Profiles | 236 | ||
| 8.3.3 Radical-based Polarizing Agents | 238 | ||
| 8.3.4 Paramagnetic Metal Ions | 240 | ||
| 8.4 Application of DNP | 242 | ||
| 8.4.1 Instrumentation | 242 | ||
| 8.4.2 Many Nuclear Species to Polarize | 245 | ||
| 8.4.3 Sample Preparation | 246 | ||
| 8.4.4 DNP in Structural Biology | 249 | ||
| 8.4.5 Conclusion and Outlook | 250 | ||
| Acknowledgements | 251 | ||
| References | 251 | ||
| Chapter 9 Paramagnetic NMR in Drug Discovery | 258 | ||
| 9.1 Introduction | 258 | ||
| 9.1.1 Pharmacological Background | 260 | ||
| 9.2 Ligand Screening | 262 | ||
| 9.2.1 Relaxation Based Methods | 262 | ||
| 9.2.2 Solvent Relaxation Method | 264 | ||
| 9.2.3 DNP-enhanced Magnetisation Transfer\rExperiments | 265 | ||
| 9.2.4 Summary | 266 | ||
| 9.3 Paramagnetic Ligands | 268 | ||
| 9.3.1 Identification and Characterisation of the Binding Site | 268 | ||
| 9.3.2 Second Site Screening with Inter-ligand PRE | 270 | ||
| 9.3.3 Paramagnetic Fragments as a Labelling Technique | 272 | ||
| 9.4 Structural Insight on Ligand–Protein Complexes | 273 | ||
| 9.4.1 Characterization of the Binding Site | 274 | ||
| 9.4.2 Ternary Complexes | 275 | ||
| 9.4.3 Structural Changes | 276 | ||
| 9.4.4 Detection of Transient Interactions of Macromolecules | 277 | ||
| 9.5 Conclusion | 278 | ||
| Acknowledgements | 279 | ||
| References | 279 | ||
| Chapter 10 Small Paramagnetic Co-solute Molecules | 283 | ||
| 10.1 Introduction | 283 | ||
| 10.2 Co-solute PRE Brought about by Translational and Rotational Modulation of the Nuclear Spin-Electron Spin Dipolar Interaction | 285 | ||
| 10.3 Paramagnetic Co-solute Molecules | 287 | ||
| 10.4 Consideration of Electron Spin Relaxation Timeson Nuclear Paramagnetic Relaxation Enhancements | 290 | ||
| 10.5 Applications of Co-solute PRE | 291 | ||
| 10.5.1 Use of Co-solute PRE to Engender Faster Data Acquisition and Sensitivity Enhancement | 291 | ||
| 10.5.2 Identification of Molecular Surfaces andBinding Interfaces in Macromolecular Complexes | 292 | ||
| 10.5.3 Biomolecular Structure Determination | 294 | ||
| 10.5.4 Determining Hydrophobic Sites in Proteins Using Dioxygen | 298 | ||
| 10.5.5 Co-solute PRE in the Study of Conformational Dynamics | 299 | ||
| 10.5.6 Co-solute Pseudocontact Shifts | 302 | ||
| 10.5.7 Small Co-solute Molecules in Applications with Lipids | 303 | ||
| 10.6 Conclusion | 304 | ||
| Acknowledgements | 304 | ||
| References | 305 | ||
| Subject Index | 310 |