Section 23.3.3.4. Helical twist and rise, and propeller twist

The helical repeat unit in Z-DNA is therefore two successive base pairs, rather than the single base pair of A- and B-DNA. Ho & Mooers (1996) propose that the C-G or ^5′pyrimidine-P-purine^3′ step be considered the fundamental unit of the Z-helical structure, because of the tight overlap between the two base pairs. As can be seen in Fig. 23.3.3.3, in a C-G step the pyrimidine rings from the two base pairs actually stack over one another, whereas the purine rings are packed against neighbouring sugar O4′ atoms. Helix-axis rotation at this step is only −8°, whereas the preceding and following G-C steps have a mammoth −52° twist. Hence, although Z-DNA has 12 base pairs per turn, it technically is not a dodecamer helix, but a hexamer with a two-base-pair repeating unit and a total rotation of −60° per unit.

This virtual restriction to purine/pyrimidine alternation means that Z-DNA cannot be involved in the coding of genetic information. A and B helices have no such restriction; their structures can accommodate a random sequence of bases. Average twist angles are as shown in Table 23.3.3.1, although extreme variation in twist is observed at individual steps in single-crystal structure analyses, from as little as 16° to as much as 55°. Base-sequence preferences for local helix parameters are discussed below.

In both B and Z helices, base pairs are very nearly perpendicular to the helix axis, whereas in the winding double ribbon of A-DNA, the long axis of each base pair is inclined by 10 to 20° away from perpendicularity to the axis. Hence, the rise per base pair for all B-helical steps and for G-C steps of Z-DNA is equal to the thickness of a base pair, 3.4 Å. The rise at a C-G step of Z-DNA is larger because it involves stacking of a sugar oxygen on each purine ring, not ring stacked on ring. For A-DNA, the rise along the helix axis can actually be less than the thickness of a base pair, because adjacent base pairs are stacked at an incline. The perpendicular distance from one base pair to the next in A-DNA is still 3.4 Å. Both A- and B-DNA exhibit considerable base pair propeller twist, especially at A·T pairs with only two hydrogen bonds rather than three. In contrast, Z-DNA, with predominately G·C pairs, shows only a small propeller twist.

The stacking of base pairs has immediate consequences for crystal growth. For Z-DNA, four base pairs are one-third of a helical turn, and six base pairs are a half turn. Hexamers are the most common crystal form in Table A23.3.1.3 by a large majority. In contrast, octamers and decamers are not simple fractions of a turn, and they stack in a disordered manner. One would predict that dodecamers of Z-DNA might crystallize well if the oligomers were not so long as to fall prey to cylindrical disorder.

By the same principles, B-DNA decamers stack easily and well to build pseudo-infinite helices through the crystal, with ordered cylindrical rods packed in six different space groups. The other common crystallization mode for B-DNA, the dodecamer, has a two-base-pair overlap of ends that both stablizes the crystals and yields a functional ten-base-pair repeat. (See Fig. 2 of Dickerson et al., 1987.) Because the dodecamers are held by their outer two base pairs, the central eight pairs are unobstructed and accessible in the crystal, making dodecamers particularly good subjects for the study of minor-groove binding drugs.

A-RNA duplexes [Table A23.3.1.1, part (k)] also stack end-for-end in a manner simulating an infinite A helix, even though the end base pairs are inclined and are not perpendicular to the helix axis. This behaviour has been seen for octamers with roughly two-thirds of a helical turn, for nonamers, and for dodecamers with roughly a full turn.

In contrast, crystals of A-DNA behave quite differently. Regardless of chain length, A-DNA helices crystallize with the outer base pair of one helix packed against one wall of the broad, open and relatively hydrophobic minor groove of another helix. This packing mode is sufficiently adaptable to accommodate duplexes of lengths four, six, eight, nine, ten and 12 base pairs. Hence, A-DNA does not simulate infinite helices through the crystal lattice, as A-RNA and B- and Z-DNA do.