CRYSTAL-STRUCTURE OF A MISPAIRED DODECAMER, D(CGAGAATTC(O(6)ME)GCG)2,CONTAINING A CARCINOGENIC O(6)-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 da ta up to 2.9-angstrom resolution. This sequence contains two mismatche d base pairs between O6-methylguanine and adenine with the arrangement A(syn).(O6-Me)G(anti) which differs from the geometry observed in sol ution by NMR. The intermolecular arrangement is equivalent to the othe r isomorphous deoxydodecamers. However, the weakening of some signific ant crystal packing contacts was observed and related to the effect of stacking between the mispaired adenine and the adjacent guanine in th e sequence. The structure is highly hydrated, with a total of 49 solve nt molecules located. The methyl group and the mismatched base-pair ge ometry locally disrupt the B-DNA-type solvent network with two solvent molecules found close to the N1 and N6 of the mispaired adenine.