C-H..O hydrogen bonds in minor groove of A-tracts in DNA double helices

Abstract

Analysis of available β-DNA type oligomeric crystal structures as well as protein-bound DNA fragments (solved using data with resolution <2.6 Å) indicates that in both data sets, a majority of the (3′-Ade) H2..O2(3′-Thy/Cyt) distances in AA.TT and GA.TC dinucleotide steps, are considerably shorter than their values in a uniform fibre model, and are smaller than their optimum separation distance. Since the electropositive C2-H2 group of adenine is in close proximity of the electronegative keto oxygen atoms of both pyrimidine bases in the antiparallel strand of the double-helical DNA structures, it suggests the possibility of intra-base-pair as well as cross-strand C-H..O hydrogen bonds in the minor groove. The C2-H2..O2 hydrogen bonds within the A.T base-pairs could be a natural consequence of Watson-Crick pairing. However, the close cross-strand interactions between the bases at the 3′-ends of the AA.TT and GA.TC steps arise due to the local sequence-dependent geometry of these steps. While the base-pair propeller twist in these steps is comparable to the fibre model, some of the other local parameters such as base-pair opening angle and inter-base-pair slide show coordinated changes, leading to these shorter C2-H2..O2 distances. Hence, in addition to the well-known minor groove hydration, it appears that favourable C2-H2..O2 cross-strand interactions may play a role in imparting a characteristic geometry to AA.TT and GA.TC steps, as well as A_n. T_n and GA_n. T_nC tracts, which leads to a narrow minor groove in these regions.