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1984 | Buch

Why Study Nucleotide and Nucleic Acid Structure? Kapitel lesen Erstes Kapitel lesen

Principles of Nucleic Acid Structure

verfasst von: Wolfram Saenger

Verlag: Springer New York

Buchreihe : Springer Advanced Texts in Chemistry

Enthalten in: Professional Book Archive

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Über dieses Buch

New textbooks at all levels of chemistry appear with great regularity. Some fields like basic biochemistry, organic reaction mechanisms, and chemical ther­ modynamics are well represented by many excellent texts, and new or revised editions are published sufficiently often to keep up with progress in research. However, some areas of chemistry, especially many of those taught at the grad­ uate level, suffer from a real lack of up-to-date textbooks. The most serious needs occur in fields that are rapidly changing. Textbooks in these subjects usually have to be written by scientists actually involved in the research which is advancing the field. It is not often easy to persuade such individuals to set time aside to help spread the knowledge they have accumulated. Our goal, in this series, is to pinpoint areas of chemistry where recent progress has outpaced what is covered in any available textbooks, and then seek out and persuade experts in these fields to produce relatively concise but instructive introductions to their fields. These should serve the needs of one semester or one quarter graduate courses in chemistry and biochemistry. In some cases the availability of texts in active research areas should help stimulate the creation of new courses. CHARLES R. CANTOR New York Preface This monograph is based on a review on polynucleotide structures written for a book series in 1976.

Inhaltsverzeichnis

Frontmatter
Chapter 1. Why Study Nucleotide and Nucleic Acid Structure?
Abstract
Before embarking on a description of nucleotide and nucleic acid structures, let us examine the biological importance of this class of molecules and find out why their structural principles should be known at the atomic level.
Wolfram Saenger
Chapter 2. Defining Terms for the Nucleic Acids
Abstract
In structural chemistry, defining the terms used to describe the geometry of molecules is fundamental in understanding basic principles. This chapter explains the conventions and nomenclature which have been adopted for nucleotides and nucleic acids. Although in nucleic acid research, atom numbering schemes and abbreviations are those recommended by the Commissions of the International Union of Pure and Applied Chemistry (IUPAC) and of the International Union of Biochemistry (IUB) (12–14), definitions of interatomic bond distances, bond angles, and torsion angles were, and still are, complex because of competing and conflicting terminology (15–18). Recently, an IUPAC-IUB subcomission worked out standard definitions (19) which will be explained and used throughout the following text.
Wolfram Saenger
Chapter 3. Methods: X-Ray Crystallography, Potential Energy Calculations, and Spectroscopy
Abstract
Nucleoside, nucleotide and nucleic acid structures have been elucidated mainly by X-ray crystallographic techniques. These methods provide information at different levels of detail depending on the molecular weight and organization of the material into crystalline or quasi-crystalline matrices. Readers not familiar with X-ray diffraction methods should be aware of the basic principles; they will then understand why the results of X-ray crystal structure analyses of small molecules up to the oligonucleotide level are unambiguous and why those of crystalline macromolecules like tRNA can, in some close details, be a matter of interpretation. Fiber diffraction analysis of quasi-crystalline polymers like DNA and RNA gives only approximate, overall structural information and cannot yield a satisfying structural model without additional data obtained by other methods.
Wolfram Saenger
Chapter 4. Structures and Conformational Properties of Bases, Furanose Sugars, and Phosphate Groups
Abstract
Because the molecular geometry and conformational properties of bases, nucleosides, and nucleotides are intrinsically related, they are discussed together in this chapter. Foundations will be laid for understanding the main structural features of the building blocks of nucleic acids which are a prerequisite for the interpretation of oligo- and polynucleotide structure. Several review articles on nucleoside and nucleotide structure and conformation have been published, describing results obtained from crystallographic studies (35,166–169) and their detailed analyses (170–172), from spectroscopic data (130,135,144,173–178) or from classical potential energy and quantum chemical calculations (70,179–182). The general physicochemical and biochemical properties of nucleosides, nucleotides, and nucleic acids are treated in several monographs and book series (123–125,183–190).
Wolfram Saenger
Chapter 5. Physical Properties of Nucleotides: Charge Densities, pK Values, Spectra, and Tautomerism
Abstract
The physical features of nucleotides discussed in this chapter will lead to an understanding of some of the characteristic properties of these molecules, especially if base-base recognition through base-pairing and base-metal interactions are concerned. Both of these processes depend on charge densities, pK values, and tautomeric states of nucleotides and are of fundamental, functional importance in biological systems.
Wolfram Saenger
Chapter 6. Forces Stabilizing Associations Between Bases: Hydrogen Bonding and Base Stacking
Abstract
Before describing structural features of nucleotides and their oligo- and polymeric complexes, a few remarks about base-base interactions are in order. These interactions are of two kinds: (a) those in the plane of the bases (horizontal) due to hydrogen bonding and (b) those perpendicular to the base planes (base stacking) stabilized mainly by London dispersion forces and hydrophobic effects. Hydrogen bonding is most pronounced in nonpolar solvents where base stacking is negligible, and base stacking dominates in water where base-base hydrogen bonding is greatly suppressed due to competition of binding sites by water molecules. Both are individually accessible to measurement and have been investigated in detail, especially hydrogen bonding because it is fundamental to the genetic code. For reviews see Refs. (448,449).
Wolfram Saenger
Chapter 7. Modified Nucleosides and Nucleotides; Nucleoside Di- and Triphosphates; Coenzymes and Antibiotics
Abstract
The modified bases, nucleosides, and nucleotides of prime concern in the present chapter are found as natural substances or are obtained synthetically. They are of importance in biochemical regulation and are used extensively in chemistry, biochemistry, and pharmacology as probes to study biological mechanisms. They have also found successful applications as antibiotics or chemotherapeutic agents. A full account of the structure and function of modified nucleosides and nucleotides would by far exceed the scope of this presentation; only a selection of the more widely known and, from a structural point of view, important molecules will be discussed here. For specialized literature, see Refs. (21,586–590).
Wolfram Saenger
Chapter 8. Metal Ion Binding to Nucleic Acids
Abstract
Nucleic acids contain four different potential sites for binding of metal ions: the negatively charged phosphate oxygen atoms, the ribose hydroxyls, the base ring nitrogens, and the exocyclic base keto groups (Figure 8–1). Because metal ions like Mg(II), Ca(II), Na(I), and K(I) are present in the body in millimolar concentrations (Table 8–1), nucleic acids and nucleotides generally occur as complexes coordinated with metal ions. These complexes are of importance for the biological action of nucleic acids, nucleotides, coenzymes, and nucleoside di- and triphosphates and are the topic of this chapter.
Wolfram Saenger
Chapter 9. Polymorphism of DNA versus Structural Conservatism of RNA: Classification of A-, B-, and Z-TYPe Double Helices
Abstract
In Chapters 10 to 15, the molecular structures of oligo- and polynucleotides are discussed together because they are intimately related. In most of the known oligonucleotide crystal structures, self-complementary, double-helical arrangements are observed. While limited in length between 2 and 12 base-pairs, these reveal fine details of polynucleotide self-assembly, hydration, and metal ion coordination. In addition, oligonucleotides sometimes crystallize as nonhelical entities with extended or looped configurations; this indicates how flexible the nucleotide building block or the phosphodiester swivel link between the individual nucleotides may be. As described in Chapter 15, the crystal structure of tRNA offers a wealth of structural information both on double-helical and on nonhelical polynucleotide domains.
Wolfram Saenger
Chapter 10. RNA Structure
Abstract
Depending on their biological function, naturally occurring RNAs either display long, double-helical structures or they are globular, with short double-helical domains connected by single-stranded stretches. Double-helical domains can, in many cases, be predicted from primary nucleotide sequences and special computer algorithms have been developed for this purpose (864). Short double helices are found in tRNA (Chapter 15), in ribosomal RNAs (865–868), in the genes coding for the coat proteins of bacteriophages MS2 (869) and R17 (870), in globin mRNA (871), and probably in other mRNAs as well (872).
Wolfram Saenger
Chapter 11. DNA Structure
Abstract
RNAs are found only in two related conformations A and A´, which both belong to the A-family double-helical structures (Chapter 10). In contrast, DNAs can adopt several other conformations depending on environmental conditions such as counterion and relative humidity and, in synthetic polynucleotides with defined, repetitive oligonucleotide building blocks, on sequence and on composition (Chapter 9). DNA double helices are classified either as A type with A-DNA the only representative or as B type encompassing B-, B´-, C-, C´-, C″-, D-, E-, and T-DNA. Besides these right-handed double helices, a left-handed variety (Z-DNA) has been discovered (Chapter 12), adding considerably to the chameleon-like, adaptable character of DNAs.
Wolfram Saenger
Chapter 12. Left-Handed, Complementary Double Helices—A Heresy? The Z-DNA Family
Abstract
Guided by X-ray fiber diagrams of DNA and RNA double helices, molecular models with right-handed screw sense were developed. Because this experimental evidence cannot, per se, distinguish between image/mirror image or right/left-handed screw molecules, in the past serious doubts as to the DNA double-helical structure have been raised (107–114). Moreover, theoretical considerations suggested that the nucleotide unit in its standard conformation can be fitted into a left-handed double-helical screw with Watson-Crick-type base-pairing (380, 383). Only in recent years has the right-handed screw structure been fully supported by means of single-crystal X-ray studies on oligonucleotides (Sections 10.4, 11.2) and tRNA (Chapter 15).
Wolfram Saenger
Chapter 13. Synthetic, Homopolymer Nucleic Acids Structures
Abstract
Looking back at Figure 6-1 reveals that base-base recognition through hydrogen bonding is not restricted to interactions between complementary bases. Like bases can also associate with themselves in a great variety of arrangements which, although thermodynamically less stable than their complementary counterparts (Section 6.4), have nevertheless been confirmed in many cases by single-crystal studies (192).
Wolfram Saenger
Chapter 14. Hypotheses and Speculations: Side-by-Side Model, Kinky DNA, and “Vertical” Double Helix
Abstract
To finish our discussion on ordered RNA and DNA helical structures, mention should be made of a few suggestions concerning their structure and dynamics. Of greatest interest among these are an alternative side-by-side model of duplex DNA which avoids twisting of one polynucleotide chain around the other and the “vertical” DNA suggested for double helices with bases in high-anti(-sc) position. Kinking of DNA was first introduced to visualize winding of the then assumed “stiff” DNA helix around the histone core in chromatin and was later extended to explain dynamic “breathing” of the DNA helix.
Wolfram Saenger
Chapter 15. tRNA—A Treasury of Stereochemical Information
Abstract
tRNA is one of the best and most thoroughly studied biological macro-molecules. Its structure-function relationships have been summarized in many books and articles (164,1027–1038), its spectroscopic behavior has been described with special reference to dynamical aspects (1027), and the thermodynamics of conformational transitions have been extensively investigated (449,554,1027,1028,1039,1040). Because discussing all of the structure-function aspects of tRNA would lead too far astray, the reader is referred to the cited literature and we focus on the questions of immediate structural interest: the primary, secondary, and tertiary structure of tRNA, the stabilization of the helical and looped domains by base stacking and base-pairing, the conformations of the nucleotides, and tRNA-metal ion interactions.
Wolfram Saenger
Chapter 16. Intercalation
Abstract
DNA, the genetic material in living cells, can interact with certain classes of drugs, carcinogens, mutagens, and dyes all of which are characterized by extended (hetero)-cyclic aromatic chromophores. Owing to DNA’s central role in biological replication and protein biosynthesis, modification by such interaction greatly alters cell metabolism, diminishing and in some cases terminating cell growth (1086–1090). These properties have generated great interest in such molecules during the past three decades. Applications in medicine have been found, and these compounds are extensively used in laboratory studies of DNA structure and function.
Wolfram Saenger
Chapter 17. Water and Nucleic Acids
Abstract
Throughout this text, the importance of water surrounding nucleic acids has been emphasized. Water is not just a medium to keep the solutes dissolved. It interacts and, in the case of macromolecules, is mainly responsible for the stabilization of secondary and tertiary structure (525,1146–1148). This holds for proteins and even more so for nucleic acids because phosphate ⋯ phosphate electrostatic repulsion is diminished by the high dielectric constant of water and hydrated counterions. Moreover, the bases self-assemble into ordered structures, and this is partly due to hydrophobic forces which again involve the active participation of water molecules. The degree of hydration of DNA plays a key role in its conformation; high relative humidity favors the B form and reduced humidity or increased ionic strength leads to a transition from the B form to C-, A-, and, if sequence permits, D- and Z-DNA.
Wolfram Saenger
Chapter 18. Protein—Nucleic Acid Interactions
Abstract
Our knowledge of interactions between proteins and nucleic acids is still rather limited. These interactions occur at all levels of DNA replication and expression and in numerous regulatory processes and are therefore of the very greatest importance in life. We do not understand how restriction endonucleases attach to DNA and cut it at specific sequences. Nor do we have a clear idea about the geometry of repressor-operator recognition. The selectivity of amino acid-tRNA synthetases for their cognate tRNAs is still obscure. The main problem is that these systems are all rather complex and require the simultaneous observation of two associated macro-molecules. Spectroscopic methods are, except for a few favorable cases, inadequate, and crystallization of protein-nucleic acid aggregates is difficult. Recently, however, two cases have been reported where specific protein-DNA (1189,1190) and protein-tRNA (1191) complexes were obtained in a form suitable for X-ray diffraction studies. We can hope, therefore, to attend the unveiling of this mystery within the next few years.
Wolfram Saenger
Chapter 19. Higher Organization of DNA
Abstract
Several forms of higher organization are known for DNA. RNA in single- or double-stranded form does not assemble into any distinctly higher ordered structure except if combined with coat proteins in viruses (Figure 18–15). For DNA, the situation is quite different. In chromatin, the DNA-protein complex constituting the chromosomes. DNA is wound around globular histone octamers to form nucleosome cores. Aligned along the DNA, these cores give chromatin the appearance of beads on a string, the string being further compacted and organized into a superhelical, solenoidal arrangement. Winding of DNA around histone octamers is associated with superhelical twisting, the topological problems of which deserve special treatment (Section 19.7).
Wolfram Saenger
Backmatter
Metadaten
Titel
Principles of Nucleic Acid Structure
verfasst von
Wolfram Saenger
Copyright-Jahr
1984
Verlag
Springer New York
Electronic ISBN
978-1-4612-5190-3
Print ISBN
978-0-387-90761-1
DOI
https://doi.org/10.1007/978-1-4612-5190-3