Section 23.3.3.3. Sugar ring conformations

Sugar ring conformations in A- and B-DNA have a logical structural basis. The B-DNA backbone is more extended than the A-DNA backbone, with P–P distances of ca 6.6 Å along one chain, compared with ca 5.5 Å in A-DNA. In turn, C2′-endo is a more extended ring conformation than C3′-endo, demonstrable in Fig. 23.3.2.4 by a greater distance between C5′ and O3′ atoms. Hence, it is logical that the more extended ring conformation should be associated with the more extended backbone chain. In Z-DNA, the extended C2′-endo form is adopted at cytosine, where a zigzag double chain reversal must be accommodated, while the more compact C3′-endo occurs at the straight backbone segment running past a guanine.

The cramped syn glycosyl conformation is strongly disfavoured, although not absolutely forbidden, at pyrimidines, most probably because of steric clash between the pyrimidine O2 and the syn ring (Haschmeyer & Rich, 1967; Davies, 1978; Ho & Mooers, 1996; Basham et al., 1998). Hence, the Z-DNA helix is effectively limited to alternating pyrimidine/purine sequences, with a price that must be paid for intermittent substitution of A and T for G and C, and an even higher price paid for breaking the pyrimidine/purine alternation. This is reflected in the X-ray crystal structures listed in Table A23.3.1.3. Only one non-alternating sequence has been completely solved and published: *C-G-G-G-*C-G (Z40), where adoption of the Z form has been forced by 5-methylation of cytosines (*C). A second non-alternating sequence that includes AT base pairs, *C-G-A-T-*C-G (Z13), was solved in 1985, but its coordinates have never been made public. It, too, required methylation of cytosines to induce the Z form. A third sequence, C-C-G-C-G-G (Z42), opens its terminal base pairs to make intermolecular base pairs with crystal neighbours. The 52 remaining Z-DNA structures in Table A23.3.1.3 all have strict alternation of pyrimidines and purines.