GUANINE-1,N-6-ETHENOADENINE BASE-PAIRS IN THE CRYSTAL-STRUCTURE OF D(CGCGAATT(EPSILON-DA)GCG)

A single-crystal X-ray analysis of the synthetic oligomer d(CGCGAATT(e psilon dA)GCG) (epsilon dA = 1,N-6-ethenoadenosine) has been carried o ut. The B-form duplex crystallizes in the orthorhombic space group P2( 1)2(1)2(1) With unit cell dimensions a = 24.31 Angstrom, b = 39.65 Ang strom, and c = 63.05 Angstrom. Refinement has converged with R = 0.182 for 2837 reflections in the resolution range 7.0-2.25 Angstrom for a model consisting of the duplex, one Mg2+ ion, and 127 water molecules. The structure contains two G.epsilon dA base pairings which adopt a G (anti).epsilon dA(syn) conformation. The geometry of the two mispairs suggests that the G.epsilon dA pairings are held together by three int erbase hydrogen bonds. These are N2(G)-H...N1(.epsilon dA), N1(G)-H... N9(epsilon dA), and O6(G)...H-C8(epsilon dA). The last interaction ser ves to alleviate the destabilizing effect that would occur due to the presence of an unfulfilled hydrogen bond acceptor. A superposition of the G(4).epsilon dA(21) base pair found in this structure and the Wats on-Crick G(4).C(21) base pair observed in the native dodecamer d(CGCGA ATTCGCG) indicates a significant difference in the sugar/phosphate bac kbone. However, the overall conformations of the two duplexes remain s imilar, suggesting that the modified base pairs are accommodated into the double helix mainly by alterations of the backbone conformation. S uch structural rearrangement of the backbone, upon incorporation of ep silon dA, may provide a signal to the 3-methyladenine-DNA glycosylase that repairs such lesions.