Crystal and Molecular Structure of a DNA Duplex Containing the Carcinogenic Lesion O⁶-Methylguanine

The crystal and molecular structure of the first DNA duplex containing the carcinogenic lesion O⁶MeG has been determined to a resolution of 1.9 Å and refined to an R factor of 19%. d[CGC- (O⁶Me)GCG]}₂ crystallizes in the left-handed Z DNA form and has crystal parameters and conformational features similar to those of the parent sequence [d(CG)₃]₂. The methyl groups on O⁶ of G4 and G10 have C⁵-C⁶-O⁶-O⁶Me torsion angles of 73° and 56°, respectively, and protrude onto the major groove surface. The base-pairing conformation for the methylated G*C base pairs is of the Watson-Crick type as opposed to a wobble-type conformation that had been proposed in a B DNA fragment. As in other Z DNA structures, a spine of hydration is seen in the minor groove.