NONINTERCALATIVE BINDING OF PROFLAVIN TO Z-DNA - STRUCTURE OF A COMPLEX BETWEEN D(5BRC-G-5BRC-G) AND PROFLAVIN

The crystal structure of a disordered 1:1 complex between the tetradeoxyoligomer d (5BrC-G-5BrC-G) and proflavin has been determined and refined to an R factor of 26.9% for 474 reflections initially in space group P65 and to an R factor of 22.2% for 475 reflections in space group P21, both at .ANG. resolution with Fobsd .gtoreq. 4.0. The unit cell constants are a = b = 17.9 .ANG., c = 44.5 .ANG., and .gamma. = 120.degree.. The final models are essentially the same in the two space groups with greater disorder in space group P65. In space group P21, the asymmetric unit is a tetranucleotide duplex, two sandwiched proflavin molecules, and four "outside-bound" proflavins. The tetranucleotide duplex is in the Z conformation and is located at the origin of the unit cell with a pair of proflavins sandwiched between the tetranucleotides. Thus, the tetranucleotides and proflavin dimers stack alternatively forming a quasi-continuous helix with the helix axis coincident with the c axis. The structure analysis revealed the presence of outside-bound proflavins as well. It is interesting that one type of outside-bound proflavins occupies a similar environment as the cobalt hexaammines in their complex with the decadeoxyoligomer d(CGTACGTACG) [Brenman, R. G., Westhof, E., and Sundaralingam, M. (1986) J. Biomol. Struct. Dyn. 3, 649]. Crystals of the latter are isomorphous to the present complex. The outside-bound proflavins penetrate the deep minor groove, thereby closing it off, and provide a visualization of a quasi-internal mode of binding of proflavin to a nucleic acid.