Direct observation of two base-pairing modes of a cytosine-thymine analogue with guanine in a DNA z-form duplex: significance for base analogue mutagenesis. [Dataset]

The pyrimidine nucleobase analogue 6H,8H-3,4-dihydropyrimido[4,5-c]-[1,2]oxazin-7-one (P) is a mimic both of cytosine and thymine, since it can form stable hydrogen-bonded base-pairs with either guanine or adenine. To investigate the geometric properties of pairing with guanine in a DNA double helix, the structure of d(CGCGPG)2 has been determined by single crystal X-ray analysis. The oligonucleotide crystallised as a left-handed Z-DNA duplex in the orthorhombic space group P212121 with cell dimensions a = 18.23 Å, b = 30.63 Å, c = 43.78 Å. Refinement using NUCLSQ with 51 water molecules included in the final model converged at R = 0.179 (Rw = 0.159) for 2798 reflections (F > 2s(F)) in the range 8 Å to 1.7 Å. Remarkably, the two P·G pairs in the hexamer duplex are different: UK Watson-Crick and wobble types separately illustrate both cytosine-like and thymine-like behaviour. The result suggests that mutagenesis experiments involving P and other analogues which display pronounced base-pairing ambivalence can be used to examine the structural basis of substrate discrimination by polymerases that is essential to accurate genetic replication. The data for this output can be found at : https://doi.org/10.2210/pdb223d/pdb