Chemistry and Biology of Non-canonical Nucleic Acids. Naoki Sugimoto
Чтение книги онлайн.
Читать онлайн книгу Chemistry and Biology of Non-canonical Nucleic Acids - Naoki Sugimoto страница 11
Название: Chemistry and Biology of Non-canonical Nucleic Acids
Автор: Naoki Sugimoto
Издательство: John Wiley & Sons Limited
Жанр: Химия
isbn: 9783527817863
isbn:
14 14 Nakano, S., Miyoshi, D., and Sugimoto, N. (2014). Chem. Rev. 114: 2733–2758.
15 15 (a) Takahashi, S. and Sugimoto, N. (2020). Chem. Soc. Rev. 49: 8439–8468.(b) Takahashi, S. and Sugimoto, N. (2021). Acc. Chem. Res. 54. In press.
2 Structures of Nucleic Acids Now
The main points of the learning:
1 Learn interactions in nucleic acid structures.
2 Understand structure polymorphisms of nucleic acids.
3 Study differences in conformational properties between DNA and RNA.
2.1 Introduction
Nucleic acids are basically molecules with a high degree of structural flexibility and polymorphic property. Phosphates in nucleic acids are negatively charged and cause electrostatic repulsion in each phosphate moiety. This electrostatic repulsion is disadvantageous for nucleic acids to form a compact and ordered structure. Nucleic acids form the higher-order structures by offsetting unfavorable entropy changes and electrostatic repulsion by internal interactions such as hydrogen bonding and stacking interactions and external factors such as interactions of nucleic acids with cations and cosolutes. In other words, the canonical nucleic acid structure consisting of double helix with Watson–Crick base pairs is a part of the possible structural forms, and nucleic acids form various non-canonical structures depending on the internal and external factors. This chapter shows basic elements that form non-canonical nucleic acid structures including unusual base pairing, whose existence has been revealed by structural analyses, and their properties of thermodynamic stabilities. Detailed analyses of the stabilities of nucleic acid structures and factors that affect them are explained in Chapter 3.
2.2 Unusual Base Pairs in a Duplex
As in Chapter 1, the canonical structure of nucleic acids is double-stranded helix with Watson–Crick base pairs (Figure 2.1), which are almost identical in their geometric and dimensional arrangement in the helix. The sugar groups are both attached to the bases on the same side of the base pair. The distance between C1′ atoms of the sugars on opposite strands is essentially the same. These geometric features enable any sequence of Watson–Crick base pairs fit into the duplex. On the other hand, a large number of other arrangements and hydrogen bonding patterns of base pairs are possible, and many have been observed experimentally such as using X-ray and NMR analyses. X-ray analysis can define the duplex structures, which incorporate the non-Watson–Crick base pairs and provide details of their hydrogen bonding scheme [1]. On the other hand, NMR analysis provides information regarding the dynamics of the nucleic acid conformation such as mismatched base pairs, in which transient tautomeric and anionic species form Watson–Crick-type hydrogen bonds [2].
Figure 2.1 Watson–Crick and Hoogsteen base pairs in double helix. Chemical structures of A-T (a) and G-C (b) Watson–Crick base pairs. Chemical structures of A-T (c) and G-C+ (d) Hoogsteen base pairs. N3 atom of cytosine nucleobase is protonated. (e) Structure of DNA duplex consisting of all A-T Hoogsteen base pairs (PDBID: 1RSB). (f) Structure of DNA duplex containing two consecutive G-C+ Hoogsteen base pairs (PDB ID: 1QN3). The DNA duplex is bending due to interaction of TATA-box binding protein. Nucleobases forming the Hoogsteen base pairs are emphasized dark. In (e) and (f), hydrogen bonds between the Hoogsteen base pairs are shown in dashed lines.
2.2.1 Hoogsteen Base Pair
Hoogsteen base pair (Figure 2.1) is one of the major non-Watson–Crick base pairs that can be seen in several crystal structures of duplexes containing A·T base pairs. For example, the crystal structure of AT-rich sequences adopted parallel and antiparallel stranded duplexes with all Hoogsteen-type hydrogen bonding in their A·T base pairs (Figure 2.1) [3]. In the case of antiparallel duplex with the Hoogsteen base pairs, the overall structure features of the duplex such as diameter of the duplex, number of base pairs per turn, and sugar pucker conformation are similar to the canonical B-type DNA duplex. A unique characteristic is that the adenine nucleobases in the duplex have syn conformation in their glycosidic bond angles. Although the same pattern of hydrogen bonding is possible, A-type RNA duplexes disfavor the A·U Hoogsteen base pair because the A-form geometry disfavors the syn conformation in the adenine nucleobase due to sugar-backbone rearrangements needed to sterically accommodate the adenine [4]. Formation of Hoogsteen-type hydrogen bonding is also possible between guanine (G) and cytosine (C+), in which N3 atom is protonated. Formation of transient Hoogsteen base pairs including the G·C+ in diverse sequence composition has been demonstrated by relaxation dispersion assay using NMR (Figure 2.1) [5]. It is considered that the Hoogsteen base pairs play roles in modulating interaction of proteins and biological reactions such as induction or repair of DNA damage and replication of DNA by altering the structural and chemical properties of the duplex [5].
2.2.2 Purine–Pyrimidine Mismatches
Mismatched base pairs between purine and pyrimidine nucleobases are known as transition mismatches. G·T and G·U mismatches can form two hydrogen bonds, which are usually known as typical “wobble” base pairs, by shifting the nucleobase geometry from that of Watson–Crick base pairs (Figure 2.2). These mismatches are one of the most stable mismatches in DNA and RNA duplexes (Tables 2.1 and 2.2). G·U base pair is frequently observed in natural RNAs. It is because that both guanine and uracil take anti conformation in their glycosidic bond angles that are the same with Watson–Crick base pairs and the distance and geometric arrangement of C1′ atoms of the sugars do not largely change compared with the canonical duplex. Thus, there is no significant worsening of base stacking and littler perturbation of the duplex conformation. Adenine and cytosine also form two hydrogen bonds as similar way as the G·T(U) mismatch when the adenine nucleobase is protonated (Figure 2.2). Formation of the A+·C mismatched base pair is demonstrated by X-ray diffraction analysis using dodecamer oligonucleotide strand [7]. However, neutral A·C mismatches are in equilibrium between the wobble and reverse wobble forms, each of which only forms one hydrogen bond. Thus, A·C mismatch is much less stable than G·T(U) mismatch in a physiological condition (Tables СКАЧАТЬ