Visualization of drug-nucleic acid interactions at atomic resolution. X. Structure of a N,N-dimethylproflavine: deoxycytidylyl(3'-5')deoxyguanosine crystalline complex.

N,N-dimethylproflavine forms a crystalline complex with deoxycytidylyl(3'-5')deoxyguanosine (d-CpG), space group P2(1)2(1)2, with a = 21.37 A, b = 34.05 A, c = 13.63 A. The structure has been solved to atomic resolution and refined by Fourier and least squares methods to a residual of 0.18 on 2,032 observed reflections. The structure consists of two N,N-dimethylproflavine molecules, two deoxycytidylyl (3'-5')deoxyguanosine molecules and 16 water molecules, a total of 128 nonhydrogen atoms. As with other structures of this type, N,N-dimethylproflavine molecules intercalate between base-paired d-CpG dimers. In addition, dimethylproflavine molecules stack on either side of the intercalated duplex, being related by a unit cell translation along the c axis. Both sugar-phosphate chains demonstrate the mixed sugar puckering geometry: C3' endo (3'-5') C2' endo. This same intercalative geometry has been seen in two other complexes containing N,N-dimethylproflavine and iodoCpG, described in the accompanying paper. Taken together, these studies indicate a common intercalative geometry present in both RNA- and DNA- model systems. Again, N,N-dimethylproflavine behaves as a simple intercalator, intercalating asymmetrically between guanine-cytosine base-pairs. The free amino- group on the intercalated dimethylproflavine molecule does not hydrogen bond directly to the phosphate oxygen. Other aspects of the structure will be presented.