Visualization of drug-nucleic acid interactions at atomic resolution

摘要: Ethidium forms a second crystalline complex with the dinucleoside monophosphate 5-iodocytidylyl(3′–5′)guanosine (iodoCpG). These crystals are monoclinic, P21, = 14.06 A, b 32.34 c 16.53 β 117.8 °. The structure has been solved to atomic resolution using rigid-body Patterson vector search and Fourier methods, refined by full matrix least-squares residual of 0.16 on 3180 observed reflections. consists two ethidium molecules, iodoCpG 27 water molecules four methanol total 165 atoms (excluding hydrogens) in asymmetric unit. Both hydrogen-bonded together guanine · cytosine Watson-Crick base-pairing. Adjacent base-pairs within this paired between neighboring adjoining unit cells separated 6.7 A. This distance reflects presence an molecule intercalated base-paired another stacked above (and below) dinucleotide. Approximate 2-fold symmetry is used interaction; pseudo-2-fold axis phenanthridinium ring system coinciding approximate relating molecules. phenyl ethyl groups lie narrow groove miniature double-helix. ethidium, however, lies opposite direction, its iodine residues. Base-pairs nucleotide units related twist about 8 magnitude angular conformational changes sugar-phosphate chains accompanying intercalation. primarily reflect differences ribose sugar puckering that (i.e. both iodocytidine residues have C3′ endo conformations, while guanosine C2′ conformations), alterations glycosidic torsional angles describe base-sugar orientation. The information provided analysis (along one (ethidium:iodoUpA), described previous paper) led understanding general nature intercalative drug binding DNA. third paper series.