Section 23.3.3.2. Glycosyl bond geometry

In both A- and B-DNA, all glycosydic bonds are anti, with sugar rings swung to either side away from the minor groove, as in Fig. 23.3.3.4(a). As mentioned earlier, when viewed into the minor groove, the backbone chains describe a clockwise rotation, with the chain on the right running downward, and that on the left upward, as in Fig. 23.3.2.1. In Z-DNA, both chains run in the opposite direction, leading to a counterclockwise rotation sense viewed into the minor groove. But Z-DNA has yet another striking (and defining) feature. Purines and pyrimidines alternate along each chain. G and C are most strongly favoured by far, but A and T can substitute intermittently at a price in stability. Breaking the strict alternation of purines and pyrimidines is even more unfavourable and is rarely encountered in crystal structures (Table A23.3.1.3). At each purine base, the glycosyl bond is rotated into the minor groove to the syn position, as in Fig. 23.3.3.4(c). This causes the local backbone directions, defined by sugar ring atoms C4′ and C3′, to be parallel in the two strands. Z-DNA avoids becoming a parallel-chain helix by performing a local chain reversal at each pyrimidine. In Fig. 23.3.3.4(c), although the local C4′–C3′ chain direction at the cytosine sugar is downward, the double loop in backbone chain gives it a net upward orientation. In stereo Fig. 23.3.3.3, the ascending backbone chain rises smoothly past each guanine, with a chain path parallel to the helix axis. However, the chain bends abruptly at right angles when passing a cytosine, in a direction tangential to the helix cylinder. Guanine sugar rings point their O4′ oxygen atoms in the backward chain direction (as is also true for all bases in A- and B-DNA), but cytosine sugars point their oxygens in the forward direction. This `up at G, across at C' pathway and inversion of sugar rings is what produces the zigzag backbone pathway that leads to the name Z-DNA. The O4′ atom of each cytosine sugar is stacked on top of the guanine ring of the subsequent nucleotide, and this stacking of a polar O (or N) on top of a polarizable aromatic ring contributes to the stability of the Z helix, as it does to many other base–base interactions to be discussed later (Bugg et al., 1971; Thomas et al., 1982; B32).

Figure 23.3.3.4| top | pdf | Glycosyl conformation and chain sense. (a) Glycosyl conformations anti/anti, backbone chains antiparallel, with clockwise sense when viewed into the minor groove, as here. This is typical for A- and B-DNA. (b) Glycosyl conformation syn/syn, backbone chains antiparallel, with counterclockwise sense viewed into minor groove. This is not known for any nucleic acid duplex. (c) Glycosyl conformation syn at G and anti at C, with the C4′—C3′ edge of the sugar pointing downward in both strands, which would seem to imply a parallel-stranded helix. However, in Z-DNA, antiparallel strands are achieved by a local reversal of chain direction at each C, as shown here. This produces the zigzag backbone pathway that is characteristic of the Z helix, visible in Fig. 23.3.3.3.