AA·TT and GA·TC dinucleotide steps in B-DNA-type oligomeric crystal structures and in protein-bound DNA fragments (solved using data with resolution <2.6 Å) show very small variations in their local dinucleotide geometries. A detailed analysis of these crystal structures reveals that in AA·TT and GA·TC steps the electropositive C2—H2 group of adenine is in very close proximity to the keto O atoms of both the pyrimidine bases in the antiparallel strand of the duplex structure, suggesting the possibility of intra-base pair as well as cross-strand inter-base pair C—H...O hydrogen bonds in the DNA minor groove. The C2—H2...O2 hydrogen bonds in the A·T base pairs could be a natural consequence of Watson–Crick pairing. However, the cross-strand interactions between the bases at the 3′-end of the AA·TT and GA·TC steps obviously arise owing to specific local geometry of these steps, since a majority of the H2...O2 distances in both data sets are considerably shorter than their values in the uniform fibre model (3.3 Å) and many are even smaller than the sum of the van der Waals radii. The analysis suggests that in addition to already documented features such as the large propeller twist of A·T base pairs and the hydration of the minor groove, these C2—H2...O2 cross-strand interactions may also play a role in the narrowing of the minor groove in A-tract regions of DNA and help explain the high structural rigidity and stability observed for poly(dA)·poly(dT).
The Thiophene “Sigma-Hole” as a Concept for Preorganized, Specific Recognition of G⋅C Base Pairs in the DNA Minor Groove