Crystal structure of a mispaired dodecamer, d(CGAGAATTC(O6Me)GCG)2, containing a carcinogenic O6-methylguanine.

The crystal structure of the synthetic deoxydodecamer d(CGAGAATTC(O6Me)GCG)2 has been determined and refined to an R-factor of 16.9% with data up to 2.9-A resolution. This sequence contains two mismatched base pairs between O6-methylguanine and adenine with the arrangement A(syn).(O6-Me)G(anti) which differs from the geometry observed in solution by NMR. The intermolecular arrangement is equivalent to the other isomorphous deoxydodecamers. However, the weakening of some significant crystal packing contacts was observed and related to the effect of stacking between the mispaired adenine and the adjacent guanine in the sequence. The structure is highly hydrated, with a total of 49 solvent molecules located. The methyl group and the mismatched base-pair geometry locally disrupt the B-DNA-type solvent network with two solvent molecules found close to the N1 and N6 of the mispaired adenine.