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Abstract
This volume focuses on solution and solid-state NMR of carbohydrates, glycoproteins, glyco-technologies, biomass and related topics. It is estimated that at least 80% of all proteins are glycoproteins. Because of the complexity, heterogeneity and flexibility of the sugar chains, the structural biology approaches for glycoconjugates have been generally avoided. NMR techniques although well established for structural analyses of proteins and nucleic acids, cannot be simply applied to this complex class of biomolecules. Nonetheless, recently developed NMR techniques for carbohydrates open the door to conformational studies of a variety of sugar chains of biological interest. NMR studies on glycans will have significant impact on the development of vaccines, adjuvants, therapeutics, biomarkers and on biomass regeneration.
In this volume, the Editors have collected the most up-to-date NMR applications from experts in the field of carbohydrate NMR spectroscopy. Timely and useful, not only for NMR specialists, it will appeal to researchers in the general field of structural biology, biochemistry and biophysics, molecular and cellular biology and material science.
Koichi Kato received his PhD in 1991 at the Graduate School of Pharmaceutical Sciences, University of Tokyo under the supervision of Professor Yoji Arata, and continued his research as Assistant Professor and Lecturer in the same institution. In 2000 he moved to Nagoya City University as full Professor and, since 2006, he has also been a Visiting Professor at the Glycoscience Institute, Ochanomizu University. In 2008 he moved to his current position at Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, holding a Professor position concurrently at Nagoya City University. His research interests include structural analyses of glycoconjugates by NMR spectroscopy and other biophysical and biochemical methods.
Thomas Peters studied chemistry at the universities of Kiel and Hamburg in Germany. In 1983 he joined the group of Professor Hans Paulsen at the University of Hamburg where he studied the synthesis and conformational analysis of N-glycan chains. Upon completion of his PhD he worked as a Postdoctoral Fellow in the laboratory of Professor David Bundle in Canada pursuing synthetic and conformational studies of bacterial antigens. In 1987 he moved to the laboratory of Professor Heinz Rüterjans, University of Frankfurt where he contributed to the development of Metropolis Monte Carlo simulations for their use in the conformational analysis of carbohydrates. Since 1994 he has held a position as Full Professor at the University of Luebeck. Ongoing research projects in his laboratory range from NMR, to protein expression, to modeling and synthesis.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Cover | Cover | ||
| NMR in Glycoscience and Glycotechnology | i | ||
| Preface | v | ||
| Contents | vii | ||
| Chapter 1 - Intramolecular Hydrogen Bonding in Glycans in Aqueous Solution | 1 | ||
| 1.1 Introduction | 1 | ||
| 1.2 NH Hydrogen Bonding | 3 | ||
| 1.3 OH Detection and Hydrogen Bonding | 7 | ||
| 1.3.1 Measuring OH Exchange Rate Constants for Inferring Hydrogen Bonding | 10 | ||
| 1.4 Hydrogen Bonding Involving C–H Bonds as Donors | 13 | ||
| 1.5 Hydrogen Bonding Between OH and Carboxylate Groups | 14 | ||
| 1.6 Future Directions | 15 | ||
| References | 17 | ||
| Chapter 2 - NMR Spin-Couplings in Saccharides: Relationships Between Structure, Conformation and the Magnitudes of JHH, JCH and JCC Values | 20 | ||
| 2.1 Introduction and Background | 21 | ||
| 2.2 Empirical Predictions of 2JCH and 2JCC Values in Saccharides | 23 | ||
| 2.3 Experimental Determinations of Spin-Coupling Signs in Saccharides | 29 | ||
| 2.4 Second-Order Behavior in 1H and 13C NMR Spectra of Saccharides | 34 | ||
| 2.5 Structural Elements of Saccharides and Factors that Influence Them | 37 | ||
| 2.5.1 Ring Conformation | 38 | ||
| 2.5.2 Exocyclic Hydroxymethyl Conformation | 40 | ||
| 2.5.3 Exocyclic C–O Bond Conformation | 41 | ||
| 2.5.4 Exocyclic N-Acetyl Group Conformation | 42 | ||
| 2.5.5 O-Glycosidic Linkage Conformation | 43 | ||
| 2.6 Assets and Limitations of J-Couplings to Determine Saccharide Structure | 44 | ||
| 2.7 Core Relationships Between J-Coupling and Saccharide Structure | 48 | ||
| 2.7.1 High Abundance of Oxygen and Nitrogen Lone-Pair Orbitals in Saccharides | 48 | ||
| 2.7.2 Two-Bond (Geminal) 13C–1H and 13C–13C Spin-Couplings | 59 | ||
| 2.7.3 Three-Bond (Vicinal) 13C–1H and 13C–13C Spin-Couplings | 63 | ||
| 2.7.4 Dual-Pathway 13C–13C Spin-Couplings in Aldopyranosyl and Aldofuranosyl Rings | 71 | ||
| 2.7.5 Four-Bond 1H–1H and 13C–1H Spin-Couplings in Aldopyranosyl Rings | 75 | ||
| 2.7.6 Spin-Couplings Across O-Glycosidic Linkages in Oligosaccharides | 83 | ||
| 2.8 Measurement of NMR Spin-Couplings in Solids | 94 | ||
| 2.9 Concluding Remarks | 95 | ||
| Acknowledgements | 97 | ||
| References | 97 | ||
| Chapter 3 - Insights into Carbohydrate Recognition by 3D Structure Determination of Protein–Carbohydrate Complexes Using NMR | 101 | ||
| 3.1 Introduction | 101 | ||
| 3.2 Overview of Protein–Carbohydrate Structures Determined by NMR | 103 | ||
| 3.3 Three-Dimensional Structure Determination by NMR Spectroscopy | 105 | ||
| 3.3.1 The Importance of Intermolecular NOEs | 105 | ||
| 3.3.2 NMR Pulse Sequences to Detect Intermolecular NOEs | 107 | ||
| 3.3.3 Isotope Labelling of Oligosaccharides | 107 | ||
| 3.3.4 Line Broadening at the Recognition Interface | 108 | ||
| 3.3.5 Binding Equilibria and Their Consequences on Detecting Intermolecular NOEs | 108 | ||
| 3.3.6 Strategies to Obtain Good Intermolecular NOEs for High Affinity Complexes | 111 | ||
| 3.3.7 Low Affinity – A Problem for Protein–Carbohydrate Structure Determination | 112 | ||
| 3.3.8 Influence of the Field Strength and Other Parameters on Intermolecular NOEs | 114 | ||
| 3.3.9 Other Complications and Solutions | 114 | ||
| 3.3.10 Promising Technological Developments Applicable to Protein–Carbohydrate Complexes | 115 | ||
| 3.4 Judging the Quality of Protein–Carbohydrate Complex Structures Determined by NMR | 116 | ||
| 3.5 Conclusions | 119 | ||
| Acknowledgements | 119 | ||
| References | 119 | ||
| Chapter 4 - Paramagnetic, RDC and RCSA Constraints in the Structural Analysis of Glycans | 123 | ||
| 4.1 Introduction | 123 | ||
| 4.2 NMR Methodology | 125 | ||
| 4.2.1 RDC and RCSA | 125 | ||
| 4.2.1.1 Theory for RDC and RCSA | 125 | ||
| 4.2.1.2 Aligning Samples for RDC and RCSA | 127 | ||
| 4.2.1.3 Measuring RDC | 128 | ||
| 4.2.1.4 Accuracy of RDC Measurement | 129 | ||
| 4.2.1.5 Measuring RCSA | 131 | ||
| 4.2.2 PCS and PRE | 131 | ||
| 4.2.2.1 PCS Theory and Measurement | 132 | ||
| 4.2.2.2 PRE Theory and Measurement | 133 | ||
| 4.3 Structure Determination | 134 | ||
| 4.4 Application to Glycan Structure and Dynamics | 136 | ||
| 4.5 Application to Glycan–Protein Complexes | 139 | ||
| References | 145 | ||
| Chapter 5 - Lanthanide-Chelating Carbohydrate Conjugates to Detect Carbohydrate–Protein Interactions | 150 | ||
| 5.1 Introduction | 150 | ||
| 5.2 Lanthanide-Chelating Carbohydrate Conjugates | 151 | ||
| 5.3 Characterization of Carbohydrate–Protein Recognition by Using Carbohydrate Conjugates Bearing Lanthanide Binding Tags | 155 | ||
| 5.4 Perspectives | 158 | ||
| References | 158 | ||
| Chapter 6 - NMR Characterization of the Conformations, Dynamics, and Interactions of Glycosphingolipids | 161 | ||
| 6.1 Introduction | 161 | ||
| 6.2 Sample Preparation for Solution NMR Experiments | 162 | ||
| 6.3 Dynamic Conformations of Ganglioside Glycans | 165 | ||
| 6.4 Ganglioside Interactions in Membrane Environments | 165 | ||
| 6.4.1 Lateral Carbohydrate Interactions | 165 | ||
| 6.4.2 Lateral Ceramide Interactions | 169 | ||
| 6.5 Ganglioside Clusters as a Platform for Protein Interactions | 171 | ||
| 6.6 Concluding Remarks | 175 | ||
| Acknowledgements | 175 | ||
| References | 176 | ||
| Chapter 7 - NMR Analysis of Glycosyltransferases | 179 | ||
| 7.1 Static Structures of Glycosyltransferases | 180 | ||
| 7.1.1 Structures from X-Ray Crystallography | 180 | ||
| 7.1.2 Structures from NMR Spectroscopy | 181 | ||
| 7.2 Dynamic Structures of Glycosyltransferases | 182 | ||
| 7.2.1 Ligand-Based NMR Experiments | 182 | ||
| 7.2.1.1 Binding Kinetics from NMR Experiments | 182 | ||
| 7.2.1.2 Enzyme Kinetics from NMR Experiments | 182 | ||
| 7.2.2 Protein-Based NMR Experiments | 184 | ||
| 7.2.2.1 Backbone Assignments of Glycosyltransferases | 186 | ||
| 7.2.2.2 Methyl Labeling of Glycosyltransferases | 186 | ||
| 7.2.2.3 Glycosyltransferase Dynamics from Relaxation Dispersion | 187 | ||
| 7.2.2.4 Glycosyltransferase Dynamics from ZZ-Exchange Experiments | 189 | ||
| 7.3 Perspectives for the Investigation of Glycosyltransferase Dynamics Using NMR Experiments | 189 | ||
| References | 191 | ||
| Chapter 8 - Stable Isotope Labeling of Glycoproteins for NMR Study | 194 | ||
| 8.1 Introduction | 194 | ||
| 8.2 Isotope Labeling of Glycoproteins Using Mammalian Expression Systems | 195 | ||
| 8.3 Glycan Labeling of Glycoproteins | 196 | ||
| 8.4 Isotope Labeling of Glycoproteins Using Non-mammalian Expression Systems | 197 | ||
| 8.4.1 Insect Cell–Silkworm Expression Systems | 197 | ||
| 8.4.2 Plant Expression Systems | 200 | ||
| 8.4.3 Yeast Expression Systems | 202 | ||
| 8.5 Concluding Remarks and Perspective | 202 | ||
| Acknowledgements | 203 | ||
| References | 205 | ||
| Chapter 9 - Quantifying Carbohydrate Motions Through Solution Measurements: Applications to Immunoglobulin G Fc | 208 | ||
| 9.1 Introduction | 208 | ||
| 9.1.1 General Glycoprotein | 208 | ||
| 9.1.2 Glycoprotein Challenges | 209 | ||
| 9.1.3 IgG1 Fc | 209 | ||
| 9.2 Methods to Prepare Labeled Glycoproteins | 211 | ||
| 9.2.1 Glycan Homogeneity is Crucial | 211 | ||
| 9.2.1.1 Genetic Manipulation of Mammalian Cells for Homogenous Glycoprotein Expression | 212 | ||
| 9.2.1.2 Chemical Manipulation of Mammalian Cells for Homogenous Glycoprotein Expression | 212 | ||
| 9.2.2 Expression-Based Methods for Polypeptide and Glycan Labeling | 212 | ||
| 9.2.2.1 Amino Acid Labeling Strategies | 213 | ||
| 9.2.2.2 Carbohydrate Labeling During Protein Expression | 213 | ||
| 9.2.3 In vitro Methods for Glycan Labeling | 213 | ||
| 9.2.3.1 Preparing Labeled Sugar Donor Substrates | 214 | ||
| 9.2.3.2 Glycosylhydrolases and Transferases | 215 | ||
| 9.3 NMR Techniques to Probe Glycan Mobility | 216 | ||
| 9.3.1 Resonance Frequencies are Sensitive to Motion | 216 | ||
| 9.3.2 Lineshape Analysis | 218 | ||
| 9.3.3 Experiments to Measure Relaxation Rates | 219 | ||
| 9.3.4 Relaxation Dispersion Methods | 219 | ||
| 9.4 Structure/Function Relationship in IgG1 Fc | 220 | ||
| 9.4.1 The IgG1 Fc N-Glycan is Mobile | 220 | ||
| 9.4.2 IgG1 Fc N-Glycan Motion is Linked to Receptor Binding Affinity | 221 | ||
| 9.4.3 Antibody N-Glycosylation Stabilizes a Critical Polypeptide Loop | 222 | ||
| 9.4.4 Fc N-Glycan Residues Distal to Asn297 Stabilize Fc | 223 | ||
| 9.5 Conclusions and Future Prospects | 224 | ||
| Acknowledgements | 224 | ||
| References | 224 | ||
| Chapter 10 - Analysis of Glycosaminoglycans by 15N-NMR Spectroscopy | 228 | ||
| 10.1 Introduction | 228 | ||
| 10.2 Characterization and Recognition of Native GAGs at Natural Abundance | 231 | ||
| 10.3 Identification of Sulfation Patterns and Position of Composing Hexosamines in GAG Disaccharides and Oligosaccharides of Diff... | 234 | ||
| 10.4 15N-Based NMR Analysis of N-Sulfonate Groups | 238 | ||
| 10.5 15N-NMR Analysis of Cellular GAGs | 244 | ||
| 10.6 Concluding Remarks | 246 | ||
| References | 247 | ||
| Chapter 11 - NMR Studies of Protein–Glycosaminoglycan Interactions | 250 | ||
| 11.1 Biology of Glycosaminoglycan | 250 | ||
| 11.2 Preparing GAG Ligands for NMR Studies | 253 | ||
| 11.3 Studying Protein-Bound GAGs | 254 | ||
| 11.4 NMR Studies of GAG-Binding Proteins | 257 | ||
| 11.5 Obtaining Intermolecular Contacts Between Protein and GAGs | 260 | ||
| 11.6 Computational Modeling of Protein–GAG Complexes Using NMR Data | 265 | ||
| References | 266 | ||
| Chapter 12 - Solid-State NMR Analysis of Mannose Recognition by Pradimicin A | 269 | ||
| 12.1 Introduction | 269 | ||
| 12.2 Underlying Problems in Interaction Analysis of Pradimicins and d-Mannose | 271 | ||
| 12.3 Analytical Strategy Using Solid-State NMR Spectroscopy | 272 | ||
| 12.4 Role of Ca2+ Ion in the Primary d-Mannose Binding of Pradimicin A | 275 | ||
| 12.5 d-Mannose Binding Geometry of Pradimicin A | 277 | ||
| 12.6 Validation of d-Mannose Binding Model of Pradimicin A | 283 | ||
| 12.7 Conclusion and Future Perspectives | 286 | ||
| Acknowledgements | 287 | ||
| References | 287 | ||
| Chapter 13 - Structure and Dynamics of Polysaccharides in Plant Cell Walls from Solid-State NMR | 290 | ||
| 13.1 2D and 3D Correlation MAS NMR Techniques for Studying Plant Cell Wall Biopolymers | 291 | ||
| 13.2 Dynamics of Polysaccharides in Primary Cell Walls | 292 | ||
| 13.2.1 Dicot Primary Cell Walls | 292 | ||
| 13.2.2 Grass Primary Cell Walls | 294 | ||
| 13.3 Cellulose Structure in Primary Cell Walls | 294 | ||
| 13.4 Polysaccharide Interactions with Other Molecules in Plant Primary Cell Walls | 296 | ||
| 13.4.1 Polysaccharide–Polysaccharide Interactions | 296 | ||
| 13.4.2 Polysaccharide–Water Interactions | 299 | ||
| 13.4.3 Polysaccharide–Protein Interactions | 300 | ||
| 13.5 Perspectives | 300 | ||
| Acknowledgements | 301 | ||
| References | 301 | ||
| Chapter 14 - New Methods for the Analysis of Heterogeneous Polysaccharides – Lessons Learned from the Heparin Crisis | 305 | ||
| 14.1 Heparin | 305 | ||
| 14.1.1 What Is Heparin | 305 | ||
| 14.1.2 The Structure of Heparin | 306 | ||
| 14.1.3 Biosynthesis | 307 | ||
| 14.1.4 Source of Heparin | 308 | ||
| 14.1.5 Manufacturing Process | 310 | ||
| 14.2 Low Molecular-Weight Heparins | 310 | ||
| 14.2.1 Production of LMWHs | 311 | ||
| 14.3 Heparin Crisis—2008 OSCS Contamination | 312 | ||
| 14.3.1 Conventional NMR Solutions to Heparin Safety | 313 | ||
| 14.3.1.1 Current Regulations | 313 | ||
| 14.3.1.2 Quantitative 2D Heteronuclear Single Quantum Correlation NMR | 314 | ||
| 14.3.2 Conventional Chemometric–NMR Solutions to Heparin Safety | 316 | ||
| 14.3.2.1 The Problem: Heterogeneous Material | 316 | ||
| 14.3.2.2 Principal Component Analysis | 317 | ||
| 14.3.2.3 Taught Analyses, Known Contaminants | 318 | ||
| 14.4 Unknown Contaminants | 319 | ||
| 14.4.1 Other Solutions—1D NMR Correlation Spectroscopy-Filtering | 319 | ||
| 14.4.1.1 Discussion of Two-Dimensional Correlation Spectroscopy | 319 | ||
| 14.4.1.2 Two-Dimensional Correlation Spectroscopy-Filtering (2D-COS-f) | 319 | ||
| 14.4.1.3 Two-Dimensional Correlation Spectroscopy-Filtering with Iterative Random Sampling (2D-COS-Firs) | 322 | ||
| 14.4.2 Correlation Spectroscopy Applied to HSQC NMR Spectra | 323 | ||
| 14.4.2.1 Statistical Sequence Information—HSQCcos of I12S-GlcNH2 Signal in Heparin | 324 | ||
| 14.4.3 Correlation Spectroscopy-Filtering Applied to HSQC NMR Spectra | 326 | ||
| 14.4.3.1 HSQCcos-f—OSCS | 327 | ||
| 14.4.3.2 HSQCcos-f—Enoxaparin | 329 | ||
| 14.5 Conclusions | 331 | ||
| Acknowledgements | 331 | ||
| References | 332 | ||
| Chapter 15 - NMR Chemical Shift Predictions and Structural Elucidation of Oligo- and Polysaccharides by the Computer Program CASPER | 335 | ||
| 15.1 Introduction | 335 | ||
| 15.2 CASPER is Based on Increment Rules | 336 | ||
| 15.2.1 CASPER Input and Output | 338 | ||
| 15.3 Structural Elucidation of a Glucan Oligosaccharide | 341 | ||
| 15.4 Structural Elucidation of a Lipopolysaccharide Having O-Acetyl Groups as Substituents | 343 | ||
| 15.5 Future Developments | 348 | ||
| Appendix 15.1 | 349 | ||
| 13C NMR chemical shifts of LPS-OH | 349 | ||
| 1H NMR chemical shifts of LPS-OH | 349 | ||
| 1H,13C-HSQC NMR chemical shifts of LPS-OH | 349 | ||
| 13C NMR chemical shifts of LPS | 349 | ||
| 1H NMR chemical shifts of LPS | 349 | ||
| 1H,13C-HSQC NMR chemical shifts of LPS | 349 | ||
| Acknowledgements | 350 | ||
| References | 350 | ||
| Chapter 16 - NMR Databases for Plant Cell Wall Biopolymers | 353 | ||
| 16.1 Introduction | 353 | ||
| 16.2 Experimental | 355 | ||
| 16.2.1 NMR Data | 355 | ||
| 16.2.2 Software Development | 355 | ||
| 16.3 Results and Discussion | 356 | ||
| 16.3.1 The Xyloglucan Oligoglycosyl Alditol Database (XGOA-DB) | 356 | ||
| 16.3.2 CeWaN—The Cell Wall NMR Database | 361 | ||
| 16.4 Conclusions | 366 | ||
| Acknowledgements | 367 | ||
| References | 367 | ||
| Chapter 17 - Polysaccharides as Major Carbon Sources in Environmental Biodiversity | 369 | ||
| 17.1 Introduction | 369 | ||
| 17.1.1 Carbon Cycle in Environmental Biodiversity | 369 | ||
| 17.1.2 Polysaccharides in Landsphere | 371 | ||
| 17.1.3 Polysaccharides in Aquasphere | 371 | ||
| 17.1.4 Contribution of NMR and Computing Techniques Toward Environmental Biodiversity | 372 | ||
| 17.2 Methodology | 372 | ||
| 17.2.1 Sample Preparation | 372 | ||
| 17.2.1.1 Stable Isotope Labeling | 373 | ||
| 17.2.1.2 Obtaining Polysaccharide Fractions | 374 | ||
| 17.2.1.3 Solubilization | 374 | ||
| 17.2.2 NMR Measurements and Data Processing | 375 | ||
| 17.2.2.1 Solution NMR | 375 | ||
| 17.2.2.2 Solid-State NMR | 375 | ||
| 17.2.2.3 Multivariate Analysis | 377 | ||
| 17.2.2.4 Theoretical Calculations | 378 | ||
| 17.3 NMR Analyses of Polysaccharides Biosynthesized by Producers | 380 | ||
| 17.3.1 NMR Approach for Land Plant Polysaccharide | 380 | ||
| 17.3.2 NMR Approach for Algae Polysaccharides | 381 | ||
| 17.4 Polysaccharides Degradation by Decomposers | 382 | ||
| 17.5 Polysaccharides as Major Energy Source in Animals and Human Beings | 384 | ||
| References | 387 | ||
| Subject Index | 396 |