Ribozymes and RNA catalysis:
Gespeichert in:
Format: | Buch |
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Sprache: | English |
Veröffentlicht: |
London
RSC Publ.
2008
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Schriftenreihe: | RSC biomolecular sciences
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Online-Zugang: | Inhaltsverzeichnis |
Beschreibung: | XX, 318 S. Ill., graph. Darst. |
ISBN: | 9780854042531 |
Internformat
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245 | 1 | 0 | |a Ribozymes and RNA catalysis |c ed. by David M. J. Lilley ... |
264 | 1 | |a London |b RSC Publ. |c 2008 | |
300 | |a XX, 318 S. |b Ill., graph. Darst. | ||
336 | |b txt |2 rdacontent | ||
337 | |b n |2 rdamedia | ||
338 | |b nc |2 rdacarrier | ||
490 | 0 | |a RSC biomolecular sciences | |
650 | 4 | |a Catalytic RNA | |
650 | 4 | |a RNA, Catalytic | |
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650 | 0 | 7 | |a Ribozym |0 (DE-588)4356469-0 |2 gnd |9 rswk-swf |
650 | 0 | 7 | |a Katalyse |0 (DE-588)4029921-1 |2 gnd |9 rswk-swf |
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689 | 1 | 1 | |a RNS |0 (DE-588)4076759-0 |D s |
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700 | 1 | |a Lilley, David M. J. |e Sonstige |4 oth | |
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Datensatz im Suchindex
_version_ | 1804137395159826433 |
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adam_text | Contents
Chapter 1 Ribozymes and RNA Catalysis: Introduction and Primer
David M.J. Lilley and Fritz Eckstein
1.1 What are Ribozymes? 1
1.2 What is the Role of Ribozymes in Cells? 1
1.3 Ribozymes Bring about Significant Rate Enhancements 4
1.4 Why Study Ribozymes? 4
1.5 Folding RNA into the Active Conformation 5
1.6 The Catalytic Resources of RNA - Making a Lot of a
Little 6
1.7 Mechanisms and Catalytic Strategies of Ribozymes 7
1.8 Impact of New Methodologies to Study Ribozymes 8
1.9 Finally 8
References 8
Chapter 2 Proton Transfer in Ribozyme Catalysis
Philip C. Bevilacqua
2.1 Scope of Chapter and Rationale 11
2.2 Overview of Proton Transfer Chemistry 12
2.3 General Considerations for Proton Transfer in RNA
Enzymes 17
2.3.1 Classes of Protonation Sites in RNA 17
2.3.2 Driving Forces for pKa Shifting in RNA 18
2.3.3 Quantitative Contributions of Proton Transfer
to RNA Catalysis 19
2.4 Proton Transfer in Small Ribozymes: Five Case
Studies 20
2.4.1 Why Small Ribozymes? 20
2.4.2 Proton Transfer in the Hepatitis Delta Virus
Ribozyme 22
2.4.3 Proton Transfer in the Hairpin Ribozyme 27
2.4.4 Proton Transfer in the Hammerhead
Ribozyme 28
xii
Contents xiii
2.4.5 Proton Transfer in the VS Ribozyme 29
2.4.6 Proton Transfer in the glmS Ribozyme 30
2.5 Conclusion and Perspectives 31
Acknowledgement 32
References 32
Chapter 3 Finding the Hammerhead Ribozyme Active Site
Dominic Lambert and John M. Burke
3.1 Introduction 37
3.2 Background 38
3.3 Experimental Data 40
3.3.1 Mechanistic Hypothesis Leads to Identifica¬
tion and Functional Test of Active Site
Components 40
3.3.2 Structural Hypothesis - Large-scale Confor-
mational Changes are Required for Catalysis 41
3.3.3 Molecular Modeling of a Hammerhead Active
Fold that Satisfies Structural and Biochemical
Constraints 43
3.4 Current Status and Future Prospects 46
Acknowledgements 46
References 46
Chapter 4 Hammerhead Ribozyme Crystal Structures and Catalysis
William G. Scott
4.1 Introduction 48
4.2 A Catalytic RNA Prototype 49
4.3 A Small Ribozyme 49
4.4 Chemistry of Phosphodiester Bond Isomerization 50
4.5 Hammerhead Ribozyme Structure 51
4.6 Catalysis in the Crystal 53
4.7 Making Movies from Crystallographic Snapshots 53
4.8 An Ever-growing List of Concerns 55
4.9 Occam s Razor Can Slit Your Throat 56
4.10 Structure of a Full-length Hammerhead Ribozyme 57
4.11 Do the Minimal and Full-length Hammerhead
Crystal Structures have Anything in Common? 59
4.12 How Does the Minimal Hammerhead Work? 60
4.13 A Movie Sequel with a Happy Ending 61
4.14 Concluding Remarks 62
Acknowledgements 62
References 62
xiv Contents
Chapter 5 The Hairpin and Varkud Satellite Ribozyntes
David M.J. Lilley
5.1 Nucleolytic Ribozymes 66
5.2 Hairpin Ribozyme 66
5.2.1 Structure of the Hairpin Ribozyme 67
5.2.2 Metal Ion-dependent Folding of the Hairpin
Ribozyme 69
5.2.3 Observing the Cleavage and Ligation Activities
of the Hairpin Ribozyme 71
5.2.4 Mechanism of the Hairpin Ribozyme 73
5.3 VS Ribozyme 76
5.3.1 Structure of the VS Ribozyme 77
5.3.2 Structure of the Substrate 80
5.3.3 Location of the Substrate 80
5.3.4 Active Site of the VS Ribozyme 82
5.3.5 Candidate Catalytic Nucleobases 82
5.3.6 Mechanism of the VS Ribozyme 84
5.4 Some Striking Similarities between the Hairpin and
VS Ribozymes 88
Acknowledgements 88
References 88
Chapter 6 Catalytic Mechanism of the HDV Ribozyme
Selene Koo, Thaddeus Novak and Joseph A. Piccirilli
6.1 Introduction 92
6.1.1 Hepatitis Delta Virus Biology 92
6.1.2 Cleavage Reactions of Small Ribozymes 93
6.2 HDV Ribozyme Structure 95
6.2.1 Determination of Crystal Structures 95
6.2.2 Structure Overview 97
6.2.3 Active Site 97
6.3 Catalytic Strategies for RNA Cleavage 99
6.4 The Active Site Nucleobase: C75 100
6.4.1 Exogenous Base Rescue Reactions 101
6.4.2 Role of C75 in HDV Catalysis 103
6.4.3 Resolving the Kinetic Ambiguity 105
6.4.3.1 Reaction in the Absence of Divalent
Cations 105
6.4.3.2 Sulfur Substitution of the Leaving
Group 106
6.5 Metal Ions in the HDV Ribozyme 108
6.5.1 Structural Metal Ions 108
6.5.2 Catalytic Metal Ions 111
Contents xv
6.6 Contributions of Non-active-site Structures to
Catalysis 112
6.7 Dynamics in HDV Function 113
6.8 Varieties of Experimental Systems 115
6.9 Models for HDV Catalysis 117
6.10 Conclusion 119
Acknowledgements 120
References 120
Chapter 7 Mammalian Self-Cleaving Ribozymes
Andrej Luptdk and Jack W. Szostak
7.1 Introduction 123
7.2 General Features of Small Self-cleaving Sequences 124
7.3 Genome-wide Selection of Self-cleaving Ribozymes 124
7.4 CPEB3 Ribozyme 125
7.4.1 Expression of the CPEB3 Ribozyme 126
7.4.2 Structural Features of the CPEB3 and HDV
Ribozymes 127
7.4.3 Linkage of HDV to the Human
Transcriptome 129
7.5 Possible Biological Roles of Self-cleaving
Ribozymes 130
7.6 Closing Remarks 131
References 131
Chapter 8 The Structure and Action of glmS Ribozymes
Kristian H. Link and Ronald R. Breaker
8.1 Introduction 134
8.2 Biochemical Characteristics of glmS Ribozymes 136
8.2.1 Divalent Metal Ions Support Structure and
Not Chemistry 136
8.2.2 Ligand Specificity of glmS Ribozymes 137
8.2.3 Evidence for a Coenzyme Role for GlcN6P 139
8.3 Atomic-resolution Structure of glmS Ribozymes 141
8.3.1 Secondary and Tertiary Structures of glmS
Ribozymes 141
8.3.2 Metabolite Recognition by glmS Ribozymes 143
8.4 Mechanism of glmS Ribozyme Self-cleavage 145
8.5 Can glmS Ribozymes be Drug Targets? 148
8.6 Conclusions 149
References 150
xvi Contents
Chapter 9 A Structural Analysis of Ribonudease P
Steven M. Marquez, Donald Evans, Alexei V. Kazantsev and
Norman R. Pace
9.1 Introduction 153
9.2 Chemistry of RNase P RNA 155
9.2.1 Universal 155
9.2.2 SN2-type Reaction 155
9.2.3 pH-Dependence of the Reaction: Hydroxide
Ion as the Nucleophile 157
9.2.4 Metal Ions in Catalysis 157
9.3 Phylogenetic Variation and Structure
of RNase P RNA 158
9.4 Early Studies of the RNase P RNA Structure 159
9.5 Crystallographic Studies of Bacterial RNase
PRNAs 160
9.6 Modeling an RNase P RNA:tRNA Complex 162
9.7 Modeling the Bacterial RNase P Holoenzyme 163
9.8 Substrate Recognition 165
9.9 Archaeal and Eucaryal Holoenzymes - More
Proteins 166
9.10 Concluding Remarks 170
Acknowledgements 171
References 171
Chapter 10 Group I Introns: Biochemical and Crystallographic
Characterization of the Active Site Structure
Barbara L. Golden
10.1 Group I Intron Origins 178
10.2 Group I Intron Self-splicing 178
10.3 What has Changed in Group I Intron Knowledge in
the Last Decade 181
10.4 Structure of Group I Introns 181
10.5 Crystallography of Group I Introns 182
10.5.1 Tetrahymena LSU P4-P6 Domain 182
10.5.2 Tetrahymena Intron Catalytic Core 183
10.5.3 Twortorf 142-12 Ribozyme 183
10.5.4 Azoarcus sp. BBH72 tRNAIle Intron 184
10.6 Structural Basis for Group I Intron Self-splicing 184
10.6.1 Recognition of the 5 -Splice Site 185
10.6.2 Does the Ribozyme Undergo Conform-
ational Changes upon PI Docking? 186
10.6.3 A Binding Pocket for Guanosine 187
10.6.4 Packed Stacks 189
Contents xvii
10.7 Biochemical Characterization of the Structure 191
10.7.1 Metal Ion Binding and Specificity Switches 191
10.7.2 Identification of Ligands to the Catalytic
Metal Ions 192
10.7.3 Correlation with Metal Ion Binding Sites
within the Crystal Structures 193
10.7.4 Nucleotide Analog Interference Techniques 194
10.8 What Makes a Catalytic Site? 196
10.9 Back to the Origins 197
References 198
Chapter 11 Group II Introns: Catalysts for Splicing, Genomic Change
and Evolution
Anna Marie Pyle
11.1 Introduction: The Place of Group II Introns Among
the Family of Ribozymes 201
11.2 The Basic Reactions of Group II Introns 201
11.3 The Biological Significance of Group II Introns 204
11.3.1 Evolutionary Significance 204
11.3.2 Significance and Prevalence in Modern
Genomes 204
11.3.3 The Potential Utility of Group II Introns 204
11.4 Domains and Parts: The Anatomy of a Group II
Intron 205
11.4.1 Domain 1 206
11.4.2 Domain 2 206
11.4.3 Domain 3 206
11.4.4 Domain 4 206
11.4.5 Domain 5 206
11.4.6 Domain 6 207
11.4.7 Other Domains and Insertions 207
11.4.8 Alternative Structural Organization and
Split Introns 208
11.5 A Big, Complicated Family: The Diversity of
Group II Introns 208
11.6 Group II Intron Tertiary Structure 209
11.7 Group II Intron Folding Mechanisms 211
11.7.1 A Slow, Direct Path to the Native State 211
11.7.2 A Folding Control Element in the Center of
Dl 212
11.7.3 Proteins and Group II Intron Folding 212
11.8 Setting the Stage for Catalysis: Proximity of the
Splice Sites and Branch-site 213
xviii Contents
11.8.1 Recognition of Exons and Ribozyme
Substrates 213
11.8.2 Branch-site Recognition and the Coordina¬
tion Loop 213
11.9 A Single Active-site for Group II Intron Catalysis 215
11.10 The Group II Intron Active-site: What are the
Players? 216
11.10.1 Active-site Players in D1 and Surrounding
Linker Regions 217
11.10.2 Domain 3 and the J2/3 Linker 217
11.10.3 Domain 5: Structural and Catalytic
Regions 218
11.11 The Chemical Mechanism of Group II Intron
Catalysis 219
11.12 Proteins and Group II Intron Function 221
11.12.1 Maturases 221
11.12.2 CRM-domain Plant Proteins 221
11.12.3 ATPase Proteins 221
11.13 Group II Introns and Their Many Hypothetical
Relatives 222
11.14 Group II Introns: RNA Processing Enzymes,
Transposons, or Tiny Living Things? 223
References 223
Chapter 12 The GIR1 Branching Ribozyme
Henrik Nielsen, Bertrand Beckert, Benoit Masquida and
Steinar D. Johansen
12.1 Introduction 229
12.2 Distribution and Structural Organization of
Twin-ribozyme Introns 231
12.3 Biological Context 234
12.3.1 Three Processing Pathways of a
Twin-ribozyme Intron 234
12.3.2 Processing of the -Dirl mRNA 235
12.3.3 Conformational Switching in GIR1 236
12.4 Biochemical Characterization 238
12.4.1 GIR1 Catalyzes Three Different Reactions 239
12.4.2 Characterization of the Branching Reaction 240
12.4.3 Biochemistry of GIR1 240
12.5 Modelling the Structure of GIR1 241
12.5.1 Overall Structure 242
12.5.2 Coaxially Stacked Helices 242
12.5.3 Junctions and Tertiary Interactions
Involving Peripheral Elements 245
Contents xix
12.5.4 The Active Site 245
12.6 Phylogenetic Considerations 247
12.7 Concluding Remarks 248
References 249
Chapter 13 Is the Spliceosome a Ribozyme?
Dipali G. Sashital and Samuel E. Butcher
13.1 Introduction 253
13.2 Similarity to Group II Self-splicing Introns 253
13.3 Role of snRNA in the Spliceosome Active Site 255
13.4 Conformation of the U2-U6 Complex and Parallels
to Group II Intron Structures 260
13.5 RNA-mediated Regulation in the Spliceosome 262
References 266
Chapter 14 Peptidyl Transferase Mechanism: The Ribosome as a
Ribozyme
Marina V. Rodnina
14.1 Introduction: Historical Background 270
14.2 The Ribosome 271
14.3 Peptidyl Transfer Reaction 272
14.3.1 Characteristics of the Reaction off the
Ribosome 273
14.3.2 Enzymology of the Peptidyl Transfer
Reaction 274
14.3.2.1 Potential Mechanisms of Rate
Acceleration by the Ribosome 274
14.3.2.2 Experimental Approaches to
Reaction on the Ribosome 275
14.3.2.3 pH-Rate Profiles 277
14.3.2.4 Activation Parameters 278
14.4 The Active Site 279
14.4.1 Structures of the Reaction Intermediates 281
14.4.2 Conformational Rearrangements of the
Active Site 282
14.4.2.1 Induced Fit 282
14.4.2.2 Role of the P-site Substrate 283
14.4.2.3 Conformational Flexibility of
the Active Site 284
14.4.3 Probing the Catalytic Mechanism: Effects
of Base Substitutions 285
14.4.4 Importance of the 2 -OH of A76 of the
P-site tRNA 286
14.5 Conclusions and Evolutionary Considerations 287
References 288
xx Contents
Chapter IS Folding Mechanisms of Group I Ribozymes
Sarah A. Woodson and Prashanth Rangan
15.1 Introduction 295
15.2 Multi-domain Architecture of Group I Ribozymes 296
15.3 RNA Folding Problem 297
15.3.1 Hierarchical Folding of tRNA 297
15.3.2 Coupling of Secondary and Tertiary
Structure 298
15.4 Late Events: Formation of Tertiary Domains in the
Tetrahymena Ribozyme 298
15.4.1 Time-resolved Footprinting of
Intermediates 298
15.4.2 Misfolding of the Intron Core 300
15.4.3 Peripheral Stability Elements 300
15.5 Kinetic Partitioning among Parallel Folding
Pathways 301
15.5.1 Theory and Experiment 301
15.5.2 Single Molecule Folding Studies 301
15.5.3 Estimating the Flux through Footprinting
Intermediates 302
15.5.4 Kinetic Partitioning In Vivo 302
15.6 Early Events: Counterion-dependent RNA Collapse 302
15.6.1 Compact Non-native Form of bI5 Ribo¬
zyme 303
15.6.2 Small Angle X-ray Scattering of Tetra¬
hymena Ribozyme 303
15.6.3 Native-like Folding Intermediates in the
Azoarcus Ribozyme 304
15.6.4 Early Folding Intermediates of the P4-P6
RNA 305
15.7 Counterions and Folding of Group I Ribozymes 305
15.7.1 Metal Ions and RNA Folding 305
15.7.2 Valence and Size of Counterions Matter 306
15.7.3 Specific Metal Ion Coordination and
Folding 307
15.8 Protein-dependent Folding of Group I Ribozymes 307
15.8.1 Stabilization of RNA Tertiary Structure 308
15.8.2 Stimulation of Refolding by RNA
Chaperones 308
15.9 Conclusion 309
References 309
Subject Index 315
|
adam_txt |
Contents
Chapter 1 Ribozymes and RNA Catalysis: Introduction and Primer
David M.J. Lilley and Fritz Eckstein
1.1 What are Ribozymes? 1
1.2 What is the Role of Ribozymes in Cells? 1
1.3 Ribozymes Bring about Significant Rate Enhancements 4
1.4 Why Study Ribozymes? 4
1.5 Folding RNA into the Active Conformation 5
1.6 The Catalytic Resources of RNA - Making a Lot of a
Little 6
1.7 Mechanisms and Catalytic Strategies of Ribozymes 7
1.8 Impact of New Methodologies to Study Ribozymes 8
1.9 Finally 8
References 8
Chapter 2 Proton Transfer in Ribozyme Catalysis
Philip C. Bevilacqua
2.1 Scope of Chapter and Rationale 11
2.2 Overview of Proton Transfer Chemistry 12
2.3 General Considerations for Proton Transfer in RNA
Enzymes 17
2.3.1 Classes of Protonation Sites in RNA 17
2.3.2 Driving Forces for pKa Shifting in RNA 18
2.3.3 Quantitative Contributions of Proton Transfer
to RNA Catalysis 19
2.4 Proton Transfer in Small Ribozymes: Five Case
Studies 20
2.4.1 Why Small Ribozymes? 20
2.4.2 Proton Transfer in the Hepatitis Delta Virus
Ribozyme 22
2.4.3 Proton Transfer in the Hairpin Ribozyme 27
2.4.4 Proton Transfer in the Hammerhead
Ribozyme 28
xii
Contents xiii
2.4.5 Proton Transfer in the VS Ribozyme 29
2.4.6 Proton Transfer in the glmS Ribozyme 30
2.5 Conclusion and Perspectives 31
Acknowledgement 32
References 32
Chapter 3 Finding the Hammerhead Ribozyme Active Site
Dominic Lambert and John M. Burke
3.1 Introduction 37
3.2 Background 38
3.3 Experimental Data 40
3.3.1 Mechanistic Hypothesis Leads to Identifica¬
tion and Functional Test of Active Site
Components 40
3.3.2 Structural Hypothesis - Large-scale Confor-
mational Changes are Required for Catalysis 41
3.3.3 Molecular Modeling of a Hammerhead Active
Fold that Satisfies Structural and Biochemical
Constraints 43
3.4 Current Status and Future Prospects 46
Acknowledgements 46
References 46
Chapter 4 Hammerhead Ribozyme Crystal Structures and Catalysis
William G. Scott
4.1 Introduction 48
4.2 A Catalytic RNA Prototype 49
4.3 A Small Ribozyme 49
4.4 Chemistry of Phosphodiester Bond Isomerization 50
4.5 Hammerhead Ribozyme Structure 51
4.6 Catalysis in the Crystal 53
4.7 Making Movies from Crystallographic Snapshots 53
4.8 An Ever-growing List of Concerns 55
4.9 Occam's Razor Can Slit Your Throat 56
4.10 Structure of a Full-length Hammerhead Ribozyme 57
4.11 Do the Minimal and Full-length Hammerhead
Crystal Structures have Anything in Common? 59
4.12 How Does the Minimal Hammerhead Work? 60
4.13 A Movie Sequel with a Happy Ending 61
4.14 Concluding Remarks 62
Acknowledgements 62
References 62
xiv Contents
Chapter 5 The Hairpin and Varkud Satellite Ribozyntes
David M.J. Lilley
5.1 Nucleolytic Ribozymes 66
5.2 Hairpin Ribozyme 66
5.2.1 Structure of the Hairpin Ribozyme 67
5.2.2 Metal Ion-dependent Folding of the Hairpin
Ribozyme 69
5.2.3 Observing the Cleavage and Ligation Activities
of the Hairpin Ribozyme 71
5.2.4 Mechanism of the Hairpin Ribozyme 73
5.3 VS Ribozyme 76
5.3.1 Structure of the VS Ribozyme 77
5.3.2 Structure of the Substrate 80
5.3.3 Location of the Substrate 80
5.3.4 Active Site of the VS Ribozyme 82
5.3.5 Candidate Catalytic Nucleobases 82
5.3.6 Mechanism of the VS Ribozyme 84
5.4 Some Striking Similarities between the Hairpin and
VS Ribozymes 88
Acknowledgements 88
References 88
Chapter 6 Catalytic Mechanism of the HDV Ribozyme
Selene Koo, Thaddeus Novak and Joseph A. Piccirilli
6.1 Introduction 92
6.1.1 Hepatitis Delta Virus Biology 92
6.1.2 Cleavage Reactions of Small Ribozymes 93
6.2 HDV Ribozyme Structure 95
6.2.1 Determination of Crystal Structures 95
6.2.2 Structure Overview 97
6.2.3 Active Site 97
6.3 Catalytic Strategies for RNA Cleavage 99
6.4 The Active Site Nucleobase: C75 100
6.4.1 Exogenous Base Rescue Reactions 101
6.4.2 Role of C75 in HDV Catalysis 103
6.4.3 Resolving the Kinetic Ambiguity 105
6.4.3.1 Reaction in the Absence of Divalent
Cations 105
6.4.3.2 Sulfur Substitution of the Leaving
Group 106
6.5 Metal Ions in the HDV Ribozyme 108
6.5.1 Structural Metal Ions 108
6.5.2 Catalytic Metal Ions 111
Contents xv
6.6 Contributions of Non-active-site Structures to
Catalysis 112
6.7 Dynamics in HDV Function 113
6.8 Varieties of Experimental Systems 115
6.9 Models for HDV Catalysis 117
6.10 Conclusion 119
Acknowledgements 120
References 120
Chapter 7 Mammalian Self-Cleaving Ribozymes
Andrej Luptdk and Jack W. Szostak
7.1 Introduction 123
7.2 General Features of Small Self-cleaving Sequences 124
7.3 Genome-wide Selection of Self-cleaving Ribozymes 124
7.4 CPEB3 Ribozyme 125
7.4.1 Expression of the CPEB3 Ribozyme 126
7.4.2 Structural Features of the CPEB3 and HDV
Ribozymes 127
7.4.3 Linkage of HDV to the Human
Transcriptome 129
7.5 Possible Biological Roles of Self-cleaving
Ribozymes 130
7.6 Closing Remarks 131
References 131
Chapter 8 The Structure and Action of glmS Ribozymes
Kristian H. Link and Ronald R. Breaker
8.1 Introduction 134
8.2 Biochemical Characteristics of glmS Ribozymes 136
8.2.1 Divalent Metal Ions Support Structure and
Not Chemistry 136
8.2.2 Ligand Specificity of glmS Ribozymes 137
8.2.3 Evidence for a Coenzyme Role for GlcN6P 139
8.3 Atomic-resolution Structure of glmS Ribozymes 141
8.3.1 Secondary and Tertiary Structures of glmS
Ribozymes 141
8.3.2 Metabolite Recognition by glmS Ribozymes 143
8.4 Mechanism of glmS Ribozyme Self-cleavage 145
8.5 Can glmS Ribozymes be Drug Targets? 148
8.6 Conclusions 149
References 150
xvi Contents
Chapter 9 A Structural Analysis of Ribonudease P
Steven M. Marquez, Donald Evans, Alexei V. Kazantsev and
Norman R. Pace
9.1 Introduction 153
9.2 Chemistry of RNase P RNA 155
9.2.1 Universal 155
9.2.2 SN2-type Reaction 155
9.2.3 pH-Dependence of the Reaction: Hydroxide
Ion as the Nucleophile 157
9.2.4 Metal Ions in Catalysis 157
9.3 Phylogenetic Variation and Structure
of RNase P RNA 158
9.4 Early Studies of the RNase P RNA Structure 159
9.5 Crystallographic Studies of Bacterial RNase
PRNAs 160
9.6 Modeling an RNase P RNA:tRNA Complex 162
9.7 Modeling the Bacterial RNase P Holoenzyme 163
9.8 Substrate Recognition 165
9.9 Archaeal and Eucaryal Holoenzymes - More
Proteins 166
9.10 Concluding Remarks 170
Acknowledgements 171
References 171
Chapter 10 Group I Introns: Biochemical and Crystallographic
Characterization of the Active Site Structure
Barbara L. Golden
10.1 Group I Intron Origins 178
10.2 Group I Intron Self-splicing 178
10.3 What has Changed in Group I Intron Knowledge in
the Last Decade 181
10.4 Structure of Group I Introns 181
10.5 Crystallography of Group I Introns 182
10.5.1 Tetrahymena LSU P4-P6 Domain 182
10.5.2 Tetrahymena Intron Catalytic Core 183
10.5.3 Twortorf 142-12 Ribozyme 183
10.5.4 Azoarcus sp. BBH72 tRNAIle Intron 184
10.6 Structural Basis for Group I Intron Self-splicing 184
10.6.1 Recognition of the 5'-Splice Site 185
10.6.2 Does the Ribozyme Undergo Conform-
ational Changes upon PI Docking? 186
10.6.3 A Binding Pocket for Guanosine 187
10.6.4 Packed Stacks 189
Contents xvii
10.7 Biochemical Characterization of the Structure 191
10.7.1 Metal Ion Binding and Specificity Switches 191
10.7.2 Identification of Ligands to the Catalytic
Metal Ions 192
10.7.3 Correlation with Metal Ion Binding Sites
within the Crystal Structures 193
10.7.4 Nucleotide Analog Interference Techniques 194
10.8 What Makes a Catalytic Site? 196
10.9 Back to the Origins 197
References 198
Chapter 11 Group II Introns: Catalysts for Splicing, Genomic Change
and Evolution
Anna Marie Pyle
11.1 Introduction: The Place of Group II Introns Among
the Family of Ribozymes 201
11.2 The Basic Reactions of Group II Introns 201
11.3 The Biological Significance of Group II Introns 204
11.3.1 Evolutionary Significance 204
11.3.2 Significance and Prevalence in Modern
Genomes 204
11.3.3 The Potential Utility of Group II Introns 204
11.4 Domains and Parts: The Anatomy of a Group II
Intron 205
11.4.1 Domain 1 206
11.4.2 Domain 2 206
11.4.3 Domain 3 206
11.4.4 Domain 4 206
11.4.5 Domain 5 206
11.4.6 Domain 6 207
11.4.7 Other Domains and Insertions 207
11.4.8 Alternative Structural Organization and
Split Introns 208
11.5 A Big, Complicated Family: The Diversity of
Group II Introns 208
11.6 Group II Intron Tertiary Structure 209
11.7 Group II Intron Folding Mechanisms 211
11.7.1 A Slow, Direct Path to the Native State 211
11.7.2 A Folding Control Element in the Center of
Dl 212
11.7.3 Proteins and Group II Intron Folding 212
11.8 Setting the Stage for Catalysis: Proximity of the
Splice Sites and Branch-site 213
xviii Contents
11.8.1 Recognition of Exons and Ribozyme
Substrates 213
11.8.2 Branch-site Recognition and the Coordina¬
tion Loop 213
11.9 A Single Active-site for Group II Intron Catalysis 215
11.10 The Group II Intron Active-site: What are the
Players? 216
11.10.1 Active-site Players in D1 and Surrounding
Linker Regions 217
11.10.2 Domain 3 and the J2/3 Linker 217
11.10.3 Domain 5: Structural and Catalytic
Regions 218
11.11 The Chemical Mechanism of Group II Intron
Catalysis 219
11.12 Proteins and Group II Intron Function 221
11.12.1 Maturases 221
11.12.2 CRM-domain Plant Proteins 221
11.12.3 ATPase Proteins 221
11.13 Group II Introns and Their Many Hypothetical
Relatives 222
11.14 Group II Introns: RNA Processing Enzymes,
Transposons, or Tiny Living Things? 223
References 223
Chapter 12 The GIR1 Branching Ribozyme
Henrik Nielsen, Bertrand Beckert, Benoit Masquida and
Steinar D. Johansen
12.1 Introduction 229
12.2 Distribution and Structural Organization of
Twin-ribozyme Introns 231
12.3 Biological Context 234
12.3.1 Three Processing Pathways of a
Twin-ribozyme Intron 234
12.3.2 Processing of the \-Dirl mRNA 235
12.3.3 Conformational Switching in GIR1 236
12.4 Biochemical Characterization 238
12.4.1 GIR1 Catalyzes Three Different Reactions 239
12.4.2 Characterization of the Branching Reaction 240
12.4.3 Biochemistry of GIR1 240
12.5 Modelling the Structure of GIR1 241
12.5.1 Overall Structure 242
12.5.2 Coaxially Stacked Helices 242
12.5.3 Junctions and Tertiary Interactions
Involving Peripheral Elements 245
Contents xix
12.5.4 The Active Site 245
12.6 Phylogenetic Considerations 247
12.7 Concluding Remarks 248
References 249
Chapter 13 Is the Spliceosome a Ribozyme?
Dipali G. Sashital and Samuel E. Butcher
13.1 Introduction 253
13.2 Similarity to Group II Self-splicing Introns 253
13.3 Role of snRNA in the Spliceosome Active Site 255
13.4 Conformation of the U2-U6 Complex and Parallels
to Group II Intron Structures 260
13.5 RNA-mediated Regulation in the Spliceosome 262
References 266
Chapter 14 Peptidyl Transferase Mechanism: The Ribosome as a
Ribozyme
Marina V. Rodnina
14.1 Introduction: Historical Background 270
14.2 The Ribosome 271
14.3 Peptidyl Transfer Reaction 272
14.3.1 Characteristics of the Reaction off the
Ribosome 273
14.3.2 Enzymology of the Peptidyl Transfer
Reaction 274
14.3.2.1 Potential Mechanisms of Rate
Acceleration by the Ribosome 274
14.3.2.2 Experimental Approaches to
Reaction on the Ribosome 275
14.3.2.3 pH-Rate Profiles 277
14.3.2.4 Activation Parameters 278
14.4 The Active Site 279
14.4.1 Structures of the Reaction Intermediates 281
14.4.2 Conformational Rearrangements of the
Active Site 282
14.4.2.1 Induced Fit 282
14.4.2.2 Role of the P-site Substrate 283
14.4.2.3 Conformational Flexibility of
the Active Site 284
14.4.3 Probing the Catalytic Mechanism: Effects
of Base Substitutions 285
14.4.4 Importance of the 2'-OH of A76 of the
P-site tRNA 286
14.5 Conclusions and Evolutionary Considerations 287
References 288
xx Contents
Chapter IS Folding Mechanisms of Group I Ribozymes
Sarah A. Woodson and Prashanth Rangan
15.1 Introduction 295
15.2 Multi-domain Architecture of Group I Ribozymes 296
15.3 RNA Folding Problem 297
15.3.1 Hierarchical Folding of tRNA 297
15.3.2 Coupling of Secondary and Tertiary
Structure 298
15.4 Late Events: Formation of Tertiary Domains in the
Tetrahymena Ribozyme 298
15.4.1 Time-resolved Footprinting of
Intermediates 298
15.4.2 Misfolding of the Intron Core 300
15.4.3 Peripheral Stability Elements 300
15.5 Kinetic Partitioning among Parallel Folding
Pathways 301
15.5.1 Theory and Experiment 301
15.5.2 Single Molecule Folding Studies 301
15.5.3 Estimating the Flux through Footprinting
Intermediates 302
15.5.4 Kinetic Partitioning In Vivo 302
15.6 Early Events: Counterion-dependent RNA Collapse 302
15.6.1 Compact Non-native Form of bI5 Ribo¬
zyme 303
15.6.2 Small Angle X-ray Scattering of Tetra¬
hymena Ribozyme 303
15.6.3 Native-like Folding Intermediates in the
Azoarcus Ribozyme 304
15.6.4 Early Folding Intermediates of the P4-P6
RNA 305
15.7 Counterions and Folding of Group I Ribozymes 305
15.7.1 Metal Ions and RNA Folding 305
15.7.2 Valence and Size of Counterions Matter 306
15.7.3 Specific Metal Ion Coordination and
Folding 307
15.8 Protein-dependent Folding of Group I Ribozymes 307
15.8.1 Stabilization of RNA Tertiary Structure 308
15.8.2 Stimulation of Refolding by RNA
Chaperones 308
15.9 Conclusion 309
References 309
Subject Index 315 |
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callnumber-search | QP623.5.C36 |
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dewey-search | 572.88 |
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discipline_str_mv | Biologie |
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id | DE-604.BV023124496 |
illustrated | Illustrated |
index_date | 2024-07-02T19:52:54Z |
indexdate | 2024-07-09T21:11:36Z |
institution | BVB |
isbn | 9780854042531 |
language | English |
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oclc_num | 183914445 |
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physical | XX, 318 S. Ill., graph. Darst. |
publishDate | 2008 |
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publisher | RSC Publ. |
record_format | marc |
series2 | RSC biomolecular sciences |
spelling | Ribozymes and RNA catalysis ed. by David M. J. Lilley ... London RSC Publ. 2008 XX, 318 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier RSC biomolecular sciences Catalytic RNA RNA, Catalytic RNS (DE-588)4076759-0 gnd rswk-swf Ribozym (DE-588)4356469-0 gnd rswk-swf Katalyse (DE-588)4029921-1 gnd rswk-swf Ribozym (DE-588)4356469-0 s DE-604 Katalyse (DE-588)4029921-1 s RNS (DE-588)4076759-0 s Lilley, David M. J. Sonstige oth HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=016326926&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
spellingShingle | Ribozymes and RNA catalysis Catalytic RNA RNA, Catalytic RNS (DE-588)4076759-0 gnd Ribozym (DE-588)4356469-0 gnd Katalyse (DE-588)4029921-1 gnd |
subject_GND | (DE-588)4076759-0 (DE-588)4356469-0 (DE-588)4029921-1 |
title | Ribozymes and RNA catalysis |
title_auth | Ribozymes and RNA catalysis |
title_exact_search | Ribozymes and RNA catalysis |
title_exact_search_txtP | Ribozymes and RNA catalysis |
title_full | Ribozymes and RNA catalysis ed. by David M. J. Lilley ... |
title_fullStr | Ribozymes and RNA catalysis ed. by David M. J. Lilley ... |
title_full_unstemmed | Ribozymes and RNA catalysis ed. by David M. J. Lilley ... |
title_short | Ribozymes and RNA catalysis |
title_sort | ribozymes and rna catalysis |
topic | Catalytic RNA RNA, Catalytic RNS (DE-588)4076759-0 gnd Ribozym (DE-588)4356469-0 gnd Katalyse (DE-588)4029921-1 gnd |
topic_facet | Catalytic RNA RNA, Catalytic RNS Ribozym Katalyse |
url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=016326926&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
work_keys_str_mv | AT lilleydavidmj ribozymesandrnacatalysis |