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Klappentext 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.The emphasis of this book concerns the origins of catalysis in RNA and is well suited for undergraduates, postgraduates and researchers in catalytic chemistry. Inhaltsverzeichnis 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. Intro...
