Ribozymes and RNA Catalysis

Herausgeber: Lilley, David M J; Eckstein, Fritz

• Gebundenes Buch

Produktbeschreibung

The emphasis of this book concerns the origins of catalysis in RNA. This necessarily includes a significant discussion of structure and folding, with the main thrust of the book being chemical mechanism. Despite the importance of RNA catalysis in the cell, its origins are still poorly understood and often controversial. RNA catalysis is important in many aspects of cell function, including RNA processing and translation. Ribozymes may hold the key to the origins of life on this planet, and can still teach us a lot about biocatalytic mechanisms in general. There has been a significant coming together in the field in recent years and this book offers a good review of the whole field.

Produktdetails

• Verlag: RSC Publishing
• Seitenzahl: 318
• Erscheinungstermin: 15. November 2007
• Englisch
• Abmessung: 234mm x 157mm x 23mm
• Gewicht: 658g
• ISBN-13: 9780854042531
• ISBN-10: 0854042539
• Artikelnr.: 23393542

Inhaltsangabe

Preface: Foreword: Twenty-five years of ribozymes
Chapter 1: Ribozymes and RNA Catalysis Introduction and Primer
1.1. What are ribozymes?
1.2. What is the role of ribozymes in cells?
1.3. Ribozymes bring about significant rate enhancements
1.4. Why study ribozymes?
1.5. Folding RNA into the active conformation
1.6. The catalytic resources of RNA - making a lot of a little
1.7. Mechanisms and catalytic strategies of ribozymes
1.8. The impact of new methodologies to study ribozymes
1.9. Finally
Chapter 2: Proton Transfer in Ribozyme Catalysis
2.1 Scope of Chapter and Rationale
2.2 Overview of Proton Transfer Chemistry
2.3 General Considerations for Proton Transfer in RNA Enzymes
2.3.1 Classes of Protonation Sites in RNA
2.3.2 Driving Forces for pKa Shifting in RNA
2.3.3 Quantitative Contributions of Proton Transfer to RNA Catalysis
2.4 Proton Transfer in Small Ribozymes: 5 case studies
2.4.1 Why Small Ribozymes?
2.4.2 Proton Transfer in the Hepatitis Delta Virus Ribozyme
2.4.3 Proton Transfer in the Hairpin Ribozyme
2.4.4 Proton Transfer in the Hammerhead Ribozyme
2.4.5 Proton Transfer in the VS Ribozyme
2.4.6 Proton Transfer in the glmS Ribozyme
2.5 Conclusion and Perspectives
2.6 References and Footnotes
Chapter 3: Finding the hammerhead active site
3.1. Introduction
3.2. Background
3.3. Experimental data
3.1.1 Mechanistic Hypothesis Leads to Identification and Functional Test of Active Site Components
3.1.2. Structural Hypothesis-Large-scale Conformational Changes are Required for Catalysis
3.1.3. Molecular Modeling of a Hammerhead Active Fold that Satisfies Structural and Biochemical Constraints
3.4. Current Status and Future Prospects
Chapter 4: Hammerhead Ribozyme Crystal Structures and Catalysis
4.1 Introduction
4.2 A Catalytic RNA Prototype
4.3 A Small Ribozyme
4.4 The Chemistry of Phosphodiester Bond Isomerization
4.5 The Hammerhead Ribozyme Structure Nailed Down
4.6 Catalysis in the Crystal
4.7 Making Movies From Crystallographic Snapshots
4.8 An Ever-Growing List of Concerns
4.9 Occam's Razor Can Slit Your Throat
4.10 The Structure of a Full-Length Hammerhead Ribozyme
4.11 Do the Minimal and Full-Length Hammerhead Crystal Structures Have Anything in Common?
4.12 How the Does the Minimal Hammerhead Work?
4.13 A Movie Sequel with a Happy Ending
4.14 Concluding remarks
Chapter 5: The Hairpin and Varkud Satellite Ribozymes
5.1. The nucleolytic ribozymes
5.2. The hairpin ribozyme
5.2.1 The structure of the hairpin ribozyme
5.2.2 Metal ion-dependent folding of the hairpin ribozyme
5.2.3 Observing the cleavage and ligation activities of the hairpin ribozyme
5.2.4 The mechanism of the hairpin ribozyme
5.3. The VS ribozyme
5.3.1 The structure of the VS ribozyme
5.3.2 The structure of the substrate
5.3.3 The location of the substrate
5.3.4 The active site of the VS ribozyme
5.3.5 Candidate catalytic nucleobases
5.3.6 The mechanism of the VS ribozyme
5.4. Some striking similarities between the hairpin and VS ribozymes
Chapter 6: Catalytic Mechanism of the HDV Ribozyme
6.1. Introduction
6.1.1. Hepatitis Delta Virus Biology
6.1.2. Cleavage Reactions of Small Ribozymes
6.2. HDV structure
6.2.1. Determination of Crystal Structures
6.2.2. Structure Overview
6.2.3. Active Site
6.3. Catalytic Strategies for RNA Cleavage
6.4. The Active Site Nucleobase: C75
6.4.1. Exogenous Base Rescue Reactions
6.4.2. The Role of C75 in HDV Catalysis
6.4.3. Resolving the Kinetic Ambiguity
6.5. Metal ions in the HDV Ribozyme
6.5.1. Structural Metal Ions
6.5.2. Catalytic Metal Ions
6.6. Contributions of Non-active-site Structures to Catalysis
6.7. Dynamics in HDV Function
6.8. Varieties of Experimental Systems
6.9. Models for HDV Catalysis
6.10. Conclusion
Chapter 7: Mammalian self-cleaving ribozymes
7.1 Introduction
7.2 General features of small self-cleaving sequences
7.3 Genome-wide selection of self-cleaving ribozymes
7.4 The CPEB3 ribozyme
7.4.1 Expression of the CPEB3 ribozyme
7.4.2 Structural features of the CPEB3 and HDV ribozymes
7.4.3 Linkage of HDV to the human transcriptome
7.5 Possible biological roles of self-cleaving ribozymes
7.6 Closing remarks
Chapter 8: The Structure and Action of glmS Ribozymes
8.1 Introduction
8.2 Biochemical characteristics of glmS ribozymes
8.2.1 Divalent metal ions support structure and not chemistry
8.2.2 Ligand specificity of glmS ribozymes
8.2.3 Evidence for a coenzyme role for GlcN6P
8.3 Atomic-resolution structure of glmS ribozymes
8.3.1 Secondary and tertiary structures of glmS ribozymes
8.3.2 Metabolite recognition by glmS ribozymes
8.4 Mechanism of glmS ribozyme self-cleavage
8.5 Can glmS ribozymes be drug targets?
8.6 Conclusions
Chapter 9: A Structural Analysis of Ribonuclease P. 9.1 Introduction
9.2 Chemistry of RNase P RNA
9.2.1 Universal
9.2.2 SN2-type reaction
9.2.3 pH-dependence of the reaction: hydroxide ion as the nucleophile
9.2.4 Metal ions in catalysis
9.3 Phylogenetic variation and structure of RNase P RNA
9.4 Early studies of the RNase P RNA structure
9.5 Crystallographic studies of bacterial RNase P RNAs
9.6 Modeling an RNase P RNA:tRNA complex
9.7 Modeling the bacterial RNase P holoenzyme
9.8 Substrate recognition
9.9 Archaeal and Eucaryal holoenzymes - more proteins
9.10 Concluding remarks
Chapter 10: Group I Introns: Biochemical and Crystallographic Characterization of the Active Site Structure
10.1. Group I intron origins
10.2 Group I intron self-splicing
10.3 What has changed in group I intron knowledge in the last decade
10.4 The structure of group I introns
10.5 Crystallography of group I introns
10.5.1 The Tetrahymena LSU P4-P6 domain
10.5.2 The Tetrahymena intron catalytic core
10.5.3 The Twort orf142-I2 ribozyme
10.5.4 The Azoarcus sp. BBH72 tRNAile intron
10.6 The structural basis for group I intron self-splicing
10.6.1 Recognition of the 5' splice site
10.6.2 Does the ribozyme undergo conformational changes upon P1 docking?
10.6.3 A binding pocket for guanosine
10.6.4 Packed stacks
10.7 Biochemical characterization of the structure
10.7.1 Metal ion binding and specificity switches
10.7.2 Identification of ligands to the catalytic metal ions
10.7.3 Correlation with metal ion binding sites within the crystal structures
10.7.4 Nucleotide analog interference techniques
10.8 What makes a catalytic site?
10.9 Back to the origins
Chapter 10: Group II introns: catalysts for splicing, genomic change and evolution
11.1 Introduction: The place of group II introns among the family of ribozymes
11.2 The basic reactions of group II introns
11.3 The biological significance of group II introns
11.3.1 Evolutionary significance
11.3.2 Significance and prevalence in modern genomes
11.4 Domains and parts: the anatomy of a group II intron
11.4.1. Domain 1
11.4.2. Domain 2
11.4.3. Domain 3
11.4.4. Domain 4
11.4.5. Domain 5
11.4.6. Domain 6
11.4.7. Other domains and insertions
11.4.8. Alternative structural organization and split introns
11.5. A big, complicated family: the diversity of group II introns
11.6. Group II intron tertiary structure
11.7. Group II intron folding mechanisms
11.7.1. A slow, direct path to the native state:
11.7.2. A folding control element in the center of D1
11.7.3. Proteins and group II intron folding
11.8 Setting the stage for catalysis: proximity of the splice sites and branch-site
11.8.1. Recognition of exons and ribozyme substrates
11.8.2. Branch-site recognition and the coordination loop
11.9. A single active-site for group II intron catalysis
11.10 The group II intron active-site: what are the players?
11.10.1. Active-site players in D1 and surrounding linker regions
11.10.2. Domain 3 and the J2/3 linker
11.10.3. Domain 5: structural and catalytic regions
11.11 The chemical mechanism of group II intron catalysis
11.12 Proteins and group II intron function
11.12.1. Maturases
11.12.2. CRM-domain plant proteins
11.12.3. ATPase proteins
11.13 Group II introns and their many hypothetical relatives
11.14 Group II introns: RNA processing enzymes, transposons, or tiny living things?
Chapter 12: The GIR1 branching ribozyme
12.1 Introduction
12.2 Distribution and structural organization of twin-ribozyme introns
12.3 The biological context
12.3.1 Three processing pathways of a twin-ribozyme intron
12.3.2 Processing of the I-DirI mRNA
12.3.3 Conformational switching in GIR1
12.4 Biochemical characterization
12.4.1 GIR1 catalyzes three different reactions
12.4.2 Characterization of the branching reaction
12.4.3 The biochemistry of GIR1
12.5 Modelling the structure of GIR1
12.5.1 The overall structure
12.5.2 Coaxially stacked helices
12.5.3 The junctions and tertiary interactions involving peripheral elements
12.5.4 The active site
12.6 Phylogenetic considerations
12.7 Concluding remarks
Chapter 13: Is the spliceosome a ribozyme?
13.1 Similarity to group II self-splicing introns
13.2 Role of snRNA in the spliceosome active site
13.3 Conformation of the U2-U6 complex and parallels to group II intron structures
13.4 RNA-mediated regulation in the spliceosome
Chapter 14: Peptidyl Transferase Mechanism: The Ribosome as a Ribozyme
14.1 Introduction: Historical background
14.2 The ribosome
14.3 The peptidyl transfer reaction
14.3.1 Characteristics of the reaction off the ribosome
14.3.2 Enzymology of the peptidyl transfer reaction
14.3.2.1 Potential mechanisms of rate acceleration by the ribosome
14.3.2.2 Experimental approaches to reaction on the ribosome
14.3.2.3 pH-rate profiles
14.3.2.4 Activation parameters
14.4 The active site
14.4.1 Structures of the reaction intermediates
14.4.2 Conformational rearragements of the active site
14.4.2.1 Induced fit
14.4.2.2 Role of the P-site substrate
14.4.2.3 Conformational flexibility of the active site
14.4.3 Probing the catalytic mechanism: Effects of base substitutions
14.4.4. Importance of the 2?-OH of A76 of the P-site tRNA
14.5 Conclusions and evolutionary considerations
Chapter 15: Folding Mechanisms of Group I Ribozymes
15.1. The multi-domain architecture of group I ribozymes
15.2. RNA Folding Problem
15.2.1 Hierarchical Folding of tRNA
15.2.2 Coupling of Secondary and Tertiary Structure
15.3. Late events: Formation of Tertiary Domains in the Tetrahymena Ribozyme
15.3.1 Time-resolved Footprinting of Intermediates
15.3.2 Misfolding of the intron core
15.3.3 Peripheral Stability Elements
15.4. Kinetic Partitioning among Parallel Folding Pathways
15.4.1 Theory and Experiment
15.4.2 Single Molecule Folding Studies
15.4.3 Estimating the Flux through Footprinting Intermediates
15.4.4. Kinetic Partitioning in vivo
15.5. Early Events: Counterion-dependent RNA collapse
15.5.1 Compact Non-Native Form of bI5 Ribozyme
15.5.2 Small Angle X-ray Scattering of Tetrahymena Ribozyme
15.5.3 Native-like Folding Intermediates in the Azoarcus Ribozyme
15.5.4 Early Folding Intermediates of the P4-P6 RNA
15.6. Counterions and Folding of Group I Ribozymes
15.6.1 Metal Ions and RNA Folding
15.6.2 Valence and Size of Counterions Matter
15.6.3 Specific Metal Ion Coordination and Folding
15.7. Protein-dependent folding of group I ribozymes
15.7.1 Stabilization of RNA Tertiary Structure
15.7.2 Stimulation of Refolding by RNA Chaperones
15.8. Conclusion