Principles of Nucleic Acid Structure (eBook)

Stephen Neidle (Autor)

eBook Download: EPUB

2010 | 1. Auflage
302 Seiten
Elsevier Science (Verlag)
978-0-08-055352-8 (ISBN)

Infos

This unique and practical resource provides the most complete and concise summary of underlying principles and approaches to studying nucleic acid structure, including discussion of x-ray crystallography, NMR, molecular modelling, and databases. Its focus is on a survey of structures especially important for biomedical research and pharmacological applications. To aid novices, Principles of Nucleic Acid Structure includes an introduction to technical lingo used to describe nucleic acid structure and conformations (roll, slide, twist, buckle, etc.). This completely updated edition features expanded coverage of the latest advances relevant to recognition of DNA and RNA by small molecules and proteins. In particular, the reader will find extensive new discussions on: RNA folding, ribosome structure and antibiotic interactions, DNA quadruplexes, DNA and RNA protein complexes, and short interfering RNA (siRNA). This handy guide ends with a complete list of resources, including relevant online databases and software. - Completely updated with expanded discussion of topics such as RNA folding, ribosome structure and antibiotic interactions, DNA quadruplexes, DNA and RNA protein complexes, and short interfering RNA (siRNA) - Includes a complete list of resources, including relevant online databases and software - Defines technical lingo for novices

Stephen Neidle is an Emeritus Professor of Chemical Biology at University College London, where he has also been the Director of Research in the School of Pharmacy. He has published over 500 primary papers and reviews and is a principal inventor on 14 patent filings. He has also written and edited several books on nucleic acids and anti-cancer drugs.

Inhalt

Front Cover 1
Principles of Nucleic Acid Structure 4
Copyright Page 5
Dedication Page 6
Preface 8
Contents 10
Chapter 1: Methods for Studying Nucleic Acid Structure 14
1.1 Introduction 14
1.2 X-ray Diffraction Methods for Structural Analysis 15
1.2.1 Overview 15
1.2.2 Fiber Diffraction Methods 18
1.2.3 Single-Crystal Methods 20
1.3 NMR Methods for Studying Nucleic Acid Structure and Dynamics 23
1.4 Molecular Modelling and Simulation of Nucleic Acids 24
1.5 Chemical, Enzymatic, and Biophysical Probes of Structure and Dynamics 27
1.6 Sources of Structural Data 28
1.7 Visualization of Nucleic Acid Molecular Structures 28
1.7.1 The Structures in This Book 29
References 29
Further Reading 30
Chapter 2: The Building-Blocks of DNA and RNA 33
2.1 Introduction 33
2.2 Base Pairing 36
2.3 Base and Base Pair Flexibility 37
2.4 Sugar Puckers 41
2.5 Conformations About the Glycosidic Bond 45
2.6 The Backbone Torsion Angles and Correlated Flexibility 46
References 49
Further Reading 50
Chapter 3: DNA Structure as Observed in Fibers and Crystals 51
3.1 Structural Fundamentals 51
3.1.1 Helical Parameters 51
3.1.2 Base-Pair Morphological Features 51
3.2 Polynucleotide Structures from Fiber Diffraction Studies 52
3.2.1 Classic DNA Structures 52
3.2.2 DNA Polymorphism in Fibers 56
3.3 B-DNA Oligonucleotide Structure as Seen in Crystallographic Analyses 60
3.3.1 The Dickerson–Drew Dodecamer 60
3.3.2 Other Studies of the Dickerson–Drew Dodecamer 62
3.3.3 Other B-DNA Oligonucleotide Structures 64
3.3.4 Sequence-Dependent Features of B-DNA: Their Occurrence and Their Prediction 69
3.4 A-DNA Oligonucleotide Crystal Structures 73
3.4.1 A-Form Octanucleotides 73
3.4.2 Do A-Form Oligonucleotides Occur in Solution? Crystal-Packing Effects 74
3.4.3 The A harr B Transition in Crystals 76
3.5 Z-DNA – Left-Handed DNA 77
3.5.1 The Z-DNA Hexanucleotide Crystal Structure 77
3.5.2 Overall Structural Features 78
3.5.3 The Z-DNA Helix 79
3.5.4 Other Z-DNA Structures 80
3.5.5 Biological Aspects of Z-DNA 80
3.6 Bent DNA 82
3.6.1 DNA Periodicity in Solution 82
3.6.2 A-Tracts and Bending 83
3.6.3 Structures Showing Bending 84
3.6.4 The Structure of Poly dAmiddotdT 86
3.7 Concluding Remarks 87
References 87
Further Reading 93
Chapter 4: Nonstandard and Higher-Order DNA Structures: DNA–DNA Recognition 94
4.1 Mismatches in DNA 94
4.1.1 General Features 94
4.1.2 Purine:Purine Mismatches 95
4.1.3 Alkylation Mismatches 98
4.2 DNA Triple Helices 101
4.2.1 Introduction 101
4.2.2 Structural Studies 103
4.2.3 Antiparallel Triplexes and Nonstandard Base-pairings 108
4.2.4 Triplex Applications 113
4.3 Guanine Quadruplexes 114
4.3.1 Introduction 114
4.3.2 Overall Structural Features of Quadruplex DNA 116
4.3.3 Examples of Simple Quadruplex Structures 120
4.3.4 Some Complex Quadruplex Structures 121
4.3.5 The i-Motif 126
4.4 DNA Junctions 127
4.4.1 Holliday Junction Structures 127
4.4.2 DNA Enzyme Structures 131
4.5 Unnatural DNA Structures 133
References 137
Further Reading 144
Chapter 5: Principles of Small Molecule-DNA Recognition 145
5.1 Introduction 145
5.2 DNA-Water Interactions 149
5.2.1 Hydration in the Grooves in Detail 153
5.3 General Features of DNA-Drug and Small-Molecule Recognition 156
5.4 Intercalative Binding 157
5.4.1 Simple Intercalators 159
5.4.2 Complex Intercalators 160
5.4.3 Major-Groove Intercalation 164
5.4.4 Bis-Intercalators 171
5.5 Intercalative-Type Binding to Higher-Order DNAs 176
5.5.1 Triplex DNA–Ligand Interactions 176
5.5.2 Ligand Binding to Quadruplex DNAs 177
5.5.3 Ligand Binding to Junction DNAs 179
5.6 Groove-Binding Molecules 182
5.6.1 Simple Groove Binding Molecules 182
5.6.2 Netropsin and Distamycin 191
5.6.3 Sequence-Specific Polyamides 195
5.7 Small Molecule Covalent Bonding to DNA 200
5.7.1 The Platinum Drugs 201
5.7.2 Covalent-Binding Combined with Sequence-Specific Recognition 204
References 208
Further Reading 215
Chapter 6: RNA Structures and Their Diversity 217
6.1 Introduction 217
6.2 Fundamentals of RNA Structure 219
6.2.1 Helical RNA Conformations 219
6.2.2 Mismatched and Bulged RNA Structures 223
6.3 Transfer RNA Structures 230
6.4 Ribozymes 234
6.4.1 The Hammerhead Ribozyme 236
6.4.2 Complex Ribozymes 237
6.5 Riboswitches 240
6.6 The Ribosome, a Ribozyme Machine 242
6.6.1 The Structure of the 30S Subunit 245
6.6.2 The Structure of the 50S subunit 247
6.6.3 Complete Ribosome Structures 247
6.7 RNA-Drug Complexes 248
6.8 RNA Motifs 254
6.9 Web Sites of Interest 256
References 257
Further Reading 261
Chapter 7: Principles of Protein-DNA Recognition 262
7.1 Introduction 262
7.2 Direct Protein-DNA Contacts 265
7.3 Major-Groove Interactions – the alpha-Helix as the Recognition Element 270
7.4 Zinc-Finger Recognition Modes 272
7.5 Other Major Groove Recognition Motifs 276
7.6 Minor-Groove Recognition 277
7.6.1 Recognition of B-DNA 277
7.6.2 The Opening-up of the Minor Groove by TBP 280
7.6.3 Other Proteins that Induce Bending of DNA 281
7.7 DNA-Bending and Protein Recognition 285
7.8 Protein-DNA-Small Molecule Recognition 288
Useful Websites 291
References 291
Further Reading 295
Index 296

Produkt-Details

• Erscheint lt. Verlag: 26.7.2010
• Sprache: englisch
• Themenwelt: Sachbuch/Ratgeber
• Themenwelt: Naturwissenschaften ► Biologie ► Biochemie
• Themenwelt: Naturwissenschaften ► Biologie ► Genetik / Molekularbiologie
• Themenwelt: Technik
• ISBN-10: 0-08-055352-4 / 0080553524
• ISBN-13: 978-0-08-055352-8 / 9780080553528