Structure of a B-form DNA/RNA chimera (dC)(rG)d(ATCG) complexed with daunomycin at 1.5 Å resolution

The crystal structure of a DNA/RNA chimera (dC)(rG)d(ATCG) complexed with the anticancer drug daunomycin has been determined at 1.5 Å resolution with R_work and R_free of 19.7 and 23.3%, respectively, for 2767 reflections. The complex crystallizes in space group P4₁2 ₁2, with unit-cell parameters a = b = 28.05, c = 53.16 Å, and contains one nucleic acid strand and one daunomycin molecule in the asymmetric unit. To our knowledge, this is the first crystal structure of a DNA/RNA chimera complexed with an intercalating drug. The DNA/RNA chimera adopts the B-form helical conformation, with the 2′-hydroxyl group in the major groove of the duplex, forming hydrogen bonds to N7 and the anionic phosphate oxygen of its 3′-side adenine. The present results indicate that the replacement by the ribose sugar in the DNA sequence does not change the geometry and intercalation pattern of daunomycin. A model of B-form RNA has been built based on the present structure. The model indicates that the interactions of the 2′-hydroxyl groups in the B-form duplex depend on their 3′-side nucleotides.