CONFORMATION OF GUANINE.8-OXOADENINE BASE-PAIRS IN THE CRYSTAL-STRUCTURE OF D(CGCGAATT(O8A)GCG)

The structure of the synthetic deoxydodecamer d(CGCGAATT(O8A)GCG)2 (O8A = 8-oxoadenine) has been determined by single-crystal X-ray diffraction techniques. The oligonucleotide crystallizes in the orthorhombic space group P2(1)2(1)2(1) with cell dimensions of a = 25.48 angstrom, b = 41.84 angstrom, and c = 64.91 angstrom. The refinement has converged with an R-factor of 0.151 for 1119 reflections in the resolution range 8.0-2.25 angstrom. Sixty-seven solvent molecules were located during the course of the refinement. The B-DNA helix consists of ten Watson-Crick base pairs and two guanine.8-oxoadenine (G.O8A) base pairs. In order to achieve hydrogen-bonding complementarity between the two bases, an unusual G(anti).O8A-(syn) wobble conformation is adopted. It is proposed that the G.O8A mispairs are held together by a network of four interbase hydrogen bonds which are the result of the formation of two reverse three-center hydrogen-bonding systems. These involve one carbonyl oxygen lone pair interacting with two hydrogen atoms. In a departure from previous observations of the characteristics of purine-purine anti.syn base pairs, lambda-1 and lambda-2, the angles between the glycosidic bonds and the C1'-C1' vector, are symmetric. Are assessment of the other purine.purine mispairs suggests that similar three-center hydrogen bonds may occur and make a contribution to stabilizing other base pairings.