Recent developments in biomolecular NMR

Library	Item Barcode	Call Number	Material Type	Item Category 1	Status
Searching... Perpustakaan Raja Zarith Sofiah	35000000000801	QD96.N8 R43 2012	Open Access Book	Book	Searching... Unknown
Searching... PSZ JB	30000010323185	QD96.N8 R43 2012	Open Access Book	Book	Searching... Unknown

NMR spectroscopy is widely used in biomolecular science particularly for structure determination of proteins, nucleic acids and carbohydrates. Much of the innovation within NMR spectroscopy has been within the field of protein NMR spectroscopy, an important technique in structural biology.

Filling a gap in the literature, this book draws together experts in the field to discuss the real advances in NMR methods that have occurred or have an impact on the biomolecular field in the last few years. The coverage includes recent developments in using NMR for determination of protein structures, membrane proteins, the dynamics of RNA and advances in NMR in drug discovery. Edited by leading biological NMR spectroscopists, the book is an essential reference for researchers in industry and academia interested in or joining this bioanalytical field.

Author Notes

Dr Marius Clore's career began at University College London where he studied for his BSc in Biochemistry, moving to University College Hospital Medical School he became an MD and finally a PhD at the National Institute for Medical Research, London. In 1984, he became head of the Biological NMR Group at Max-Planck Institute for Biochemistry and then moved in 1988 to NIH, USA. He is currently an NIH Distinguished Investigator and Chief of the Protein Nuclear Magnetic Resonance Section and has made many pioneering contributions in the development of NMR spectroscopy for structural characterization of biological macromolecules. Dr Clore has been awarded numerous prizes and honours and was ranked in the top 20 in h-index ranking of living chemists in 2009. He is also a 3rd Degree black belt in Tae Kwon Do.

Dr Jennifer Potts studied at the University of Sydney before becoming a postdoctoral fellow at the University of Oxford in 1992. Staying at Oxford until 2005 as a research associate and latterly lecturer in biochemistry, she then became Anniversary Reader at the University of York where her recent work has been on fibronectin recognition domains which fold on experiencing their target.

Michael J. Plevin and Jérôme BoisbouvierKoh Takeuchi and Maayan Gal and Ichio Shimada and Gerhard WagnerR William BroadhurstOliver F. LangeH. Jane DysonJesika T. Schilder and Mathias A. S. Hass and Peter H. J. Keizers and Marcellus UbbinkSean K. Whittier and J. Patrick LoriaLoïc Salmon and Phineus Markwick and Martin BlackledgeCatherine D. Eichhorn and Shan Yang and Hashim M. Al-HashimiErik R. P. ZuiderwegCarine Farenc and Gregg SiegalMark Bostock and Daniel NietlispachVictoria A. Higman and Anthony Watts

Chapter 1 Isotope-Labelling of Methyl Groups for NMR Studies of Large Proteins	p. 1
1.1 Introduction-Large Proteins and Solution NMR Spectroscopy	p. 1
1.1.1 Isotope-Labelling and Protein NMR Spectroscopy	p. 1
1.1.2 General Considerations for NMR Studies of Larger Proteins	p. 2
1.1.3 NMR Experiments Designed for Larger Systems	p. 4
1.2 Using Methyl Groups as Probes for NMR Spectroscopy	p. 6
1.2.1 Why the Methyl Group?	p. 6
1.2.2 Strategies for Selective Protonation of Methyl Groups in Perdeuterated Proteins	p. 6
1.3 Strategies for Sequence-Specific Resonance Assignment in High Molecular Weight Proteins	p. 13
1.3.1 Resonance Assignment of Large Proteins by 'Divide and Conquer'	p. 14
1.3.2 Resonance Assignment by Mutagenesis	p. 16
1.3.3 Time Frames for Resonance Aassignment of Methyl Groups in Very Large Proteins	p. 17
1.4 High Molecular Weight Protein Applications of Methyl-Specific Isotope-Labelling	p. 18
1.5 Conclusions and Future Directions	p. 18
Acknowledgements	p. 21
References	p. 22
Chapter 2 Low-¿ Nuclei Detection Experiments for Biomolecular NMR	p. 25
2.1 Introduction	p. 25
2.2 Relaxation Properties of Low-¿ Nuclei	p. 28
2.3 Management of One-Bond Couplings in Low-¿ Detection Experiments	p. 31
2.4 C ¿ -Detection Experiments for Main-Chain Resonance Assignments	p. 35
2.5 15 N H -Detection Experiments for Main-Chain Resonance Assignments	p. 43
2.6 Low-¿ Detection in Interaction Studies and Structure Determination	p. 46
2.7 Conclusion	p. 47
Acknowledgements	p. 48
References	p. 49
Chapter 3 Making the Most of Chemical Shifts	p. 53
3.1 Introduction	p. 53
3.2 The Chemical Shift Tensor	p. 54
3.3 Referencing, Databases and Re-referencing	p. 56
3.4 Reference States and Secondary Chemical Shifts	p. 58
3.5 Detecting Structure and Flexibility	p. 60
3.6 Predicting Dihedral Angles	p. 63
3.7 Predicting Isotropic Chemical Shifts from Atomic Coordinates	p. 66
3.8 Predicting Tertiary Structure from Chemical Shifts	p. 69
3.9 Predicting Quaternary Structure from Chemical Shifts	p. 72
3.10 Conclusions	p. 76
Acknowledgements	p. 76
References	p. 76
Chapter 4 Protein Structure Determination using Sparse NMR Data	p. 84
4.1 Introduction	p. 84
4.2 Force-Fields	p. 88
4.2.1 Introduction to Force-Fields	p. 88
4.2.2 Hybrid Molecular Mechanics Force-Fields	p. 88
4.2.3 The ROSETTA All-Atom Force-Field	p. 88
4.2.4 Relaxing the Structure	p. 90
4.2.5 ROSETTA All-Atom Force-Field Accuracy	p. 90
4.3 NMR Restraints	p. 92
4.3.1 Nuclear Overhauser Effect	p. 92
4.3.2 Residual Dipolar Coupling	p. 96
4.3.3 Paramagnetic Relaxation Enhancement	p. 97
4.3.4 Pseudo-Contact Chemical Shifts	p. 98
4.3.5 Chemical Shift	p. 99
4.4 Optimization Methods	p. 101
4.4.1 Challenges for Optimisation Methods	p. 101
4.4.2 Top-Down vs. Bottom-Up	p. 102
4.4.3 Resolution-Adapted Structural Recombination	p. 103
4.5 Concluding Remarks	p. 104
Acknowledgements	p. 105
References	p. 105
Chapter 5 NMR Studies of Disordered but Functional Proteins	p. 111
5.1 Introduction	p. 111
5.2 NMR Methods Used for Disordered Proteins	p. 112
5.3 Coupled Folding and Binding	p. 112
5.3.1 Folded and Unfolded CBP Domains Bind IDP Partners	p. 113
5.3.2 The NF¿B-I¿B¿ Interaction: Fold/Unfold Symphony	p. 117
5.3.3 Binding Without Folding	p. 121
5.4 Partly Folded and Molten Globule-Like States	p. 121
5.4.1 Ankyrin Repeat Proteins	p. 121
5.4.2 Binding-Induced Molten Globule-Like States	p. 122
5.5 Functional Disorder in Folded States	p. 122
5.5.1 Sequence Specificity of Zinc-Finger Proteins	p. 122
5.5.2 Effects of Alternative Splicing	p. 124
5.6 Conclusions	p. 125
References	p. 125
Chapter 6 Paramagnetic NMR Spectroscopy and Lowly Populated States	p. 130
6.1 Introduction	p. 130
6.1.1 Lowly Populated States and Paramagnetic NMR Spectroscopy	p. 130
6.1.2 Paramagnetic Centers	p. 131
6.1.3 Ensemble Modelling	p. 133
6.2 Residual Dipolar Coupling and Pseudo-Contact Shifts	p. 133
6.2.1 RDC Theory	p. 133
6.2.2 PCS Theory	p. 134
6.2.3 Applications for Studying Lowly Populated States	p. 135
6.3 Paramagnetic Relaxation Enhancement	p. 135
6.3.1 PRE Theory	p. 135
6.3.2 Applications for Studying Lowly Populated States	p. 138
6.4 Relaxation Dispersion	p. 142
6.4.1 RD Theory	p. 142
6.4.2 Applications for Studying Lowly Populated States	p. 144
6.5 Conclusion and Future Perspectives	p. 145
References	p. 145
Chapter 7 NMR Relaxation Dispersion Studies of Large Enzymes in Solution	p. 151
7.1 Introduction	p. 151
7.2 Conformational Exchange	p. 152
7.3 The Benefits of TROSY	p. 155
7.3.1 1 H- 15 N TROSY	p. 155
7.3.2 Methyl-TROSY	p. 157
7.4 Isotopic Labelling Strategies	p. 159
7.5 Applications	p. 159
7.5.1 Imidazole Glycerol Phosphate Synthase	p. 159
7.5.2 Triosephosphate Isomerase	p. 161
7.6 Conclusions	p. 162
Acknowledgements	p. 162
References	p. 162
Chapter 8 Residual Dipolar Couplings as a Tool for the Study of Protein Conformation and Conformational Flexibility	p. 166
8.1 Introduction	p. 166
8.2 Residual Dipolar Couplings as Probes of Protein Conformation	p. 168
8.3 Residual Dipolar Couplings for Structure Determination	p. 169
8.4 Residual Dipolar Couplings for the Study of Protein Dynamics	p. 170
8.4.1 Domain Dynamics	p. 171
8.4.2 Local Backbone Dynamics	p. 171
8.5 Conclusions	p. 180
References	p. 180
Chapter 9 Characterising RNA Dynamics using NMR Residual Dipolar Couplings	p. 184
9.1 Introduction	p. 184
9.2 Residual Dipolar Coupling Theory	p. 185
9.2.1 The Dipolar Interaction	p. 185
9.2.2 The Alignment Tensor	p. 187
9.3 Partial Alignment of Nucleic Acids	p. 188
9.3.1 Ordering Media-Induced Alignment	p. 189
9.3.2 Magnetic-Field-Induced Alignment	p. 192
9.4 Measurement of RDCs in Nucleic Acids	p. 193
9.5 Dynamic Interpretation of RDCs Measured in RNA	p. 197
9.5.1 Dynamics Information Contained Within RDCs	p. 197
9.5.2 Decoupling Internal and Overall Motions by Domain Elongation	p. 199
9.5.3 Inter-Helical Motions from Order Tensor Analysis of RDCs	p. 201
9.5.4 Constructing Dynamic Ensembles	p. 202
9.5.5 Explicit Treatment of Motional Couplings	p. 204
9.6 Example Applications in Studies of RNA Dynamics From RDCs	p. 205
9.7 Summary and Future Perspectives	p. 208
Acknowledgements	p. 209
References	p. 209
Chapter 10 Non-Canonical Ligand-Binding Events as Detected by NMR	p. 216
10.1 A Brief Refresher on NMR-Focussed Ligand Binding	p. 216
10.1.1 Ligand Binding Thermodynamics and Kinetics	p. 216
10.1.2 Ligand Binding and NMR	p. 218
10.2 The Proton Ligands to Inositol Hexakis Phosphate Take Five Instead of Three Log Units to Complete Binding	p. 221
10.3 The Binding of Inositol Hexakis Phosphate to Hemoglobin: Fast-Exchange Kinetics for Nanomolar Affinity	p. 226
10.4 Non-Canonical Line Broadening in Slow Exchange after Equivalence is Reached	p. 235
10.5 Binding of a 10 kDa Ligand to a 70 kDa Protein Does not Result in Significant Line Broadening of the NMR Signals of the 10 kDa Ligand	p. 242
10.5.1 A View From the DnaJ Perspective	p. 242
10.5.2 A View from the DnaK Perspective	p. 247
10.5.3 Relevance of the J-Domain-DnaK Complex	p. 248
Acknowledgements	p. 251
References	p. 252
Chapter 11 Recent Advances in Biomolecular NMR for Drug Discovery	p. 254
11.1 Introduction	p. 254
11.2 NMR for Ligand Discovery	p. 255
11.2.1 Protein-Observed NMR	p. 255
11.2.2 Ligand-Observed NMR	p. 257
11.3 Hit Prioritisation	p. 261
11.4 Protein-Ligand Structures	p. 262
11.5 In-Cell NMR Spectroscopy	p. 266
11.6 Perspectives	p. 267
References	p. 267
Chapter 12 NMR of Membrane Proteins	p. 271
12.1 Introduction	p. 271
12.2 Protein Expression	p. 273
12.2.1 Escherichia coli	p. 273
12.2.2 Yeast	p. 274
12.2.3 Baculovirus/Insect Expression	p. 275
12.2.4 Mammalian	p. 276
12.2.5 Cell-Free Expression	p. 276
12.2.6 Directed Evolution	p. 278
12.3 Membrane Mimics	p. 278
12.3.1 Detergents	p. 278
12.3.2 Fluorinated Surfactants	p. 283
12.3.3 Amphipols	p. 284
12.3.4 Problems with Micelles	p. 285
12.3.5 Nanolipoprotein Particles	p. 286
12.3.6 NMR Studies using Nanodiscs	p. 287
12.3.7 Bicelles	p. 287
12.4 Isotope-Labelling Strategies	p. 289
12.5 Structure Determination	p. 292
12.5.1 Paramagnetic Effects	p. 293
12.5.2 Residual Dipolar Couplings	p. 295
12.5.3 Chemical Shift Prediction	p. 297
12.6 NMR Method Development	p. 298
12.6.1 13 C Direct Detection	p. 298
12.6.2 Alternative Sampling	p. 299
12.7 Functional Information	p. 300
12.7.1 Dynamics	p. 300
12.7.2 Variation of Experimental Conditions	p. 301
12.7.3 Ligand-Binding Studies	p. 301
12.8 Conclusions	p. 303
References	p. 304
Chapter 13 Recent Developments in Biomolecular Solid-State NMR	p. 318
13.1 Introduction	p. 318
13.2 Samples	p. 319
13.3 Assignment Strategies	p. 322
13.4 Labelling Strategies	p. 322
13.5 Structure Determination	p. 323
13.6 Dynamics	p. 324
13.7 Static Solid-State NMR	p. 325
13.8 Proton Detection	p. 325
13.9 Ultra-Fast Spinning	p. 326
13.10 Dynamic Nuclear Polarisation	p. 326
13.11 Approaches Using Complementary Techniques	p. 328
13.12 Conclusions and Perspectives	p. 328
References	p. 329
Subject Index	p. 335

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