Structure of the side-by-side binding of distamycin to d(GTATATAC)(2)

The 2.40 Angstrom resolution crystal structure of a side-by-side binding of distamycin A molecules to a DNA octamer d(GTATATAC)(2) with an extended al ternating TA sequence has been determined. The unit-cell parameters are a = 29.55, b = 42.18, c = 43.38 Angstrom, B = 96.56 degrees, space group P2(1) , with two molecules in the asymmetric unit, in contrast to ail previous si de-by-side distamycin-DNA complexes which have only a single DNA strand and one drug molecule in the asymmetric unit. The structure was solved by the molecular-replacement method and refined to an R index of 21.0% using 3467 reflections [greater than or equal to 2 sigma(F)]. The minor grooves of the DNA molecules bind two side-by-side antiparallel staggered distamycins spa nning about five base pairs and virtually covering the entire length of the DNA. The octamer duplexes exhibit low-high alternations in the helical twi st, sugar puckering and the C-O3' and O3'-P torsion angles, similar to the earlier side-by-side complexes containing inosine bases. The molecules are stacked one over the other along the ac diagonal in an infinite pseudo-cont inuous helical column with no lateral interactions.