Biological Chemistry - Berezov T. T., Korovkin B. F. 1998

Chemistry of Nucleic Acids
Structure of Nucleic Acids
Secondary Structure of Nucleic Acids

According to the model proposed by J. Watson and F. Crick in 1953 based on a series of analytical data as well as X-Ray Diffraction Analysis, the DNA molecule consists of two chains forming a right-handed helix, in which both polynucleotide strands are wound around the same axis. The strands are held together by Hydrogen Bonds formed between their nitrogenous bases (Fig. 3.1). Both polynucleotide strands in the double-helical DNA molecule have a strictly defined spatial arrangement in which the nitrogenous bases are located on the inside, while the phosphoryl and carbohydrate components are on the outside*.

A detailed analysis of various options for Hydrogen bond formation between the bases showed that in the double-helical DNA molecule, the bases are arranged in pairs: a purine from one strand and a pyrimidine from the other, in accordance with Chargaff's rules. Since the orientation of the bases in a plane is evidently not arbitrary, and the bases in polynucleotides occur in the lactam form, the adenine–thymine and guanine–cytosine pairs were recognized as the most probable. This pairing mechanism subsequently received experimental confirmation. The selectivity of A–T and G–C pair interactions is commonly expressed by the term "complementarity," and the corresponding nitrogenous bases are referred to as complementary. The stability of A–T Base Pairs is provided by two hydrogen bonds, and that of G–C pairs by three, which in turn is determined by the specific arrangement of the Functional groups of the nitrogenous bases. The length of the hydrogen bonds between the bases is about 0.3 nm. Thus, not only individual bases prove to be complementary, but the deoxyribonucleotide strands of DNA AS A whole, contributing to The formation of a highly compact Structure and the stabilization of the entire molecule*.

* For this discovery, J. Watson and F. Crick, together with M. Wilkins, were awarded the Nobel Prize in 1962.

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Fig. 3.1. Schematic representation of the DNA double helix.

a - according to Watson and Crick: c - deoxyribose residue, p - phosphoric acid residue; b - A-form of DNA; c - B-form of DNA.

Both strands in the DNA molecule have opposite polarity. This means that the internucleotide bond in one strand has a 5’→3’ direction, and in the other, a 3'→5' direction. Such orientation of the strands is of vital biological importance during METABOLISM/36.html">DNA Replication and Transcription.

* Data obtained in recent years indicate that hydrophobic interactions between complementary bases stacking in the center of The Double Helix play the primary role in stabilizing the double-helical structure. Hydrogen bonds most likely ensure the Specificity of base pairing.

The DNA model (see Fig. 3.1) shows that the distance between turns (the pitch of the helix) is 3.4 nm. This segment accommodates 10 nucleotide residues, the size of a single nucleotide is 0.34 nm, and the diameter of the double-helical molecule is 1.8 nm.

It should be noted that the configuration of the DNA double helix varies greatly depending on the quantitative Water content and the Ionic strength of the surrounding environment. X-ray diffraction Methods have proven the existence of at least 6 forms of DNA, designated as the A-, B-, C-, D-, E-, and Z-forms. The configurations of two of these in their simplest form are presented in Fig. 3.1, b and c. It can be seen that the A-form exhibits a slight Displacement of the base pairs from the molecular axis toward the periphery, which affects its dimensions (2.8 nm is the length of a single turn, which contains 11 mononucleotides instead of 10; the distance between NUCLEOTIDES changes, etc.). While the A- and B-forms represent a right-handed double helix, the Z-form (zigzag) of DNA has a left-handed configuration in which the phosphodiester backbone is arranged in a zigzag pattern along the molecular axis. Parallel to the phosphodiester backbone in The structure of the A- and B-forms of DNA, there are Major and minor grooves—sites where Proteins bind, evidently performing regulatory Functions during Gene Expression. Currently, there is reason to believe that mutual transitions occur between the A- and B-forms of DNA upon changes in salt concentration and the degree of Hydration. The B-form of DNA corresponds most closely to the Watson-Crick model. These transitions, which can be induced by Solvents or proteins, undoubtedly possess a certain biological significance. It is hypothesized that in the A-form, DNA serves as a template in the transcription process (RNA Synthesis on a DNA molecule), whereas in the B-form, it acts as a template in the replication process (DNA Synthesis on a DNA molecule).

In the structure of DNA, as well as in RNA, nucleotide sequences known as "palindromes," or inverted repeats, have been discovered. They occur both within a single strand and in the double helix. For instance, like the word rotator, which reads the same from right to left and vice versa. Such inverted repeats can serve as the basis for the formation of hairpin structures or other variations with altered intrastrand and interstrand pairing, resulting in the formation of triple-helical regions. It is possible that these palindromic structures have a specific biological significance in regulating the expression of individual genes, serving as sites for DNA-binding proteins. However, considerable efforts are still required both to establish the exact structure of these variations and to determine their functional role.

The Introduction/11.html">Secondary structure of messenger and Ribosomal RNAs is less well characterized. Regarding the secondary structure of tRNA, the most plausible model is the one proposed by R. Holley, whose two-dimensional representation resembles a cloverleaf (see Fig. 14.3). At present, with the Primary Structure of most tRNAs known, The sequence of all or nearly all natural tRNAs appears to fit into this "cloverleaf" scheme (see Chapter 14). Comparing these structures reveals A number of regularities that undoubtedly have specific biological significance. All tRNAs contain regions that interact with Ribosomes, sites for binding Amino Acids and Enzymes, and a specific sequence of three nucleotides (a triplet) called the anticodon, which is complementary to the trinucleotide sequence of mRNA (the codon) that codes for the incorporation of a specific amino acid into the protein molecule.

Regardless of the type of RNA, the transcription product synthesized in The Cell (see Chapter 13) is always represented by a single strand, which is folded into a secondary structure not randomly, but in accordance with the DNA program. Because RNA contains free 2'-hydroxyl groups of ribose not involved in standard Watson-Crick base pairing, additional opportunities arise for the Formation of secondary and tertiary structures containing bulges, hairpins, or cruciform structures. The Structural Features of tRNA are directly related to the Translation process; therefore, they are discussed in more detail in the section on Protein Biosynthesis (Chapter 14).