Neidle Principles of Nucleic Acid Structure

1. Auflage 2010
ISBN: 978-0-08-055352-8
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 302 Seiten

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.

Autoren/Hrsg.

Neidle, Stephen

Inhaltsverzeichnis

1;Front Cover;1
2;Principles of Nucleic Acid Structure;4
3;Copyright Page;5
4;Dedication Page;6
5;Preface;8
6;Contents;10
7;Chapter 1: Methods for Studying Nucleic Acid Structure;14
7.1;1.1 Introduction;14
7.2;1.2 X-ray Diffraction Methods for Structural Analysis;15
7.2.1;1.2.1 Overview;15
7.2.2;1.2.2 Fiber Diffraction Methods;18
7.2.3;1.2.3 Single-Crystal Methods;20
7.3;1.3 NMR Methods for Studying Nucleic Acid Structure and Dynamics;23
7.4;1.4 Molecular Modelling and Simulation of Nucleic Acids;24
7.5;1.5 Chemical, Enzymatic, and Biophysical Probes of Structure and Dynamics;27
7.6;1.6 Sources of Structural Data;28
7.7;1.7 Visualization of Nucleic Acid Molecular Structures;28
7.7.1;1.7.1 The Structures in This Book;29
7.8;References;29
7.9;Further Reading;30
8;Chapter 2: The Building-Blocks of DNA and RNA;33
8.1;2.1 Introduction;33
8.2;2.2 Base Pairing;36
8.3;2.3 Base and Base Pair Flexibility;37
8.4;2.4 Sugar Puckers;41
8.5;2.5 Conformations About the Glycosidic Bond;45
8.6;2.6 The Backbone Torsion Angles and Correlated Flexibility;46
8.7;References;49
8.8;Further Reading;50
9;Chapter 3: DNA Structure as Observed in Fibers and Crystals;51
9.1;3.1 Structural Fundamentals;51
9.1.1;3.1.1 Helical Parameters;51
9.1.2;3.1.2 Base-Pair Morphological Features;51
9.2;3.2 Polynucleotide Structures from Fiber Diffraction Studies;52
9.2.1;3.2.1 Classic DNA Structures;52
9.2.2;3.2.2 DNA Polymorphism in Fibers;56
9.3;3.3 B-DNA Oligonucleotide Structure as Seen in Crystallographic Analyses;60
9.3.1;3.3.1 The Dickerson–Drew Dodecamer;60
9.3.2;3.3.2 Other Studies of the Dickerson–Drew Dodecamer;62
9.3.3;3.3.3 Other B-DNA Oligonucleotide Structures;64
9.3.4;3.3.4 Sequence-Dependent Features of B-DNA: Their Occurrence and Their Prediction;69
9.4;3.4 A-DNA Oligonucleotide Crystal Structures;73
9.4.1;3.4.1 A-Form Octanucleotides;73
9.4.2;3.4.2 Do A-Form Oligonucleotides Occur in Solution? Crystal-Packing Effects;74
9.4.3;3.4.3 The A harr B Transition in Crystals;76
9.5;3.5 Z-DNA – Left-Handed DNA;77
9.5.1;3.5.1 The Z-DNA Hexanucleotide Crystal Structure;77
9.5.2;3.5.2 Overall Structural Features;78
9.5.3;3.5.3 The Z-DNA Helix;79
9.5.4;3.5.4 Other Z-DNA Structures;80
9.5.5;3.5.5 Biological Aspects of Z-DNA;80
9.6;3.6 Bent DNA;82
9.6.1;3.6.1 DNA Periodicity in Solution;82
9.6.2;3.6.2 A-Tracts and Bending;83
9.6.3;3.6.3 Structures Showing Bending;84
9.6.4;3.6.4 The Structure of Poly dAmiddotdT;86
9.7;3.7 Concluding Remarks;87
9.8;References;87
9.9;Further Reading;93
10;Chapter 4: Nonstandard and Higher-Order DNA Structures: DNA–DNA Recognition;94
10.1;4.1 Mismatches in DNA;94
10.1.1;4.1.1 General Features;94
10.1.2;4.1.2 Purine:Purine Mismatches;95
10.1.3;4.1.3 Alkylation Mismatches;98
10.2;4.2 DNA Triple Helices;101
10.2.1;4.2.1 Introduction;101
10.2.2;4.2.2 Structural Studies;103
10.2.3;4.2.3 Antiparallel Triplexes and Nonstandard Base-pairings;108
10.2.4;4.2.4 Triplex Applications;113
10.3;4.3 Guanine Quadruplexes;114
10.3.1;4.3.1 Introduction;114
10.3.2;4.3.2 Overall Structural Features of Quadruplex DNA;116
10.3.3;4.3.3 Examples of Simple Quadruplex Structures;120
10.3.4;4.3.4 Some Complex Quadruplex Structures;121
10.3.5;4.3.5 The i-Motif;126
10.4;4.4 DNA Junctions;127
10.4.1;4.4.1 Holliday Junction Structures;127
10.4.2;4.4.2 DNA Enzyme Structures;131
10.5;4.5 Unnatural DNA Structures;133
10.6;References;137
10.7;Further Reading;144
11;Chapter 5: Principles of Small Molecule-DNA Recognition;145
11.1;5.1 Introduction;145
11.2;5.2 DNA-Water Interactions;149
11.2.1;5.2.1 Hydration in the Grooves in Detail;153
11.3;5.3 General Features of DNA-Drug and Small-Molecule Recognition;156
11.4;5.4 Intercalative Binding;157
11.4.1;5.4.1 Simple Intercalators;159
11.4.2;5.4.2 Complex Intercalators;160
11.4.3;5.4.3 Major-Groove Intercalation;164
11.4.4;5.4.4 Bis-Intercalators;171
11.5;5.5 Intercalative-Type Binding to Higher-Order DNAs;176
11.5.1;5.5.1 Triplex DNA–Ligand Interactions;176
11.5.2;5.5.2 Ligand Binding to Quadruplex DNAs;177
11.5.3;5.5.3 Ligand Binding to Junction DNAs;179
11.6;5.6 Groove-Binding Molecules;182
11.6.1;5.6.1 Simple Groove Binding Molecules;182
11.6.2;5.6.2 Netropsin and Distamycin;191
11.6.3;5.6.3 Sequence-Specific Polyamides;195
11.7;5.7 Small Molecule Covalent Bonding to DNA;200
11.7.1;5.7.1 The Platinum Drugs;201
11.7.2;5.7.2 Covalent-Binding Combined with Sequence-Specific Recognition;204
11.8;References;208
11.9;Further Reading;215
12;Chapter 6: RNA Structures and Their Diversity;217
12.1;6.1 Introduction;217
12.2;6.2 Fundamentals of RNA Structure;219
12.2.1;6.2.1 Helical RNA Conformations;219
12.2.2;6.2.2 Mismatched and Bulged RNA Structures;223
12.3;6.3 Transfer RNA Structures;230
12.4;6.4 Ribozymes;234
12.4.1;6.4.1 The Hammerhead Ribozyme;236
12.4.2;6.4.2 Complex Ribozymes;237
12.5;6.5 Riboswitches;240
12.6;6.6 The Ribosome, a Ribozyme Machine;242
12.6.1;6.6.1 The Structure of the 30S Subunit;245
12.6.2;6.6.2 The Structure of the 50S subunit;247
12.6.3;6.6.3 Complete Ribosome Structures;247
12.7;6.7 RNA-Drug Complexes;248
12.8;6.8 RNA Motifs;254
12.9;6.9 Web Sites of Interest;256
12.10;References;257
12.11;Further Reading;261
13;Chapter 7: Principles of Protein-DNA Recognition;262
13.1;7.1 Introduction;262
13.2;7.2 Direct Protein-DNA Contacts;265
13.3;7.3 Major-Groove Interactions – the alpha-Helix as the Recognition Element;270
13.4;7.4 Zinc-Finger Recognition Modes;272
13.5;7.5 Other Major Groove Recognition Motifs;276
13.6;7.6 Minor-Groove Recognition;277
13.6.1;7.6.1 Recognition of B-DNA;277
13.6.2;7.6.2 The Opening-up of the Minor Groove by TBP;280
13.6.3;7.6.3 Other Proteins that Induce Bending of DNA;281
13.7;7.7 DNA-Bending and Protein Recognition;285
13.8;7.8 Protein-DNA-Small Molecule Recognition;288
13.9;Useful Websites;291
13.10;References;291
13.11;Further Reading;295
14;Index;296