154d
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DNA DISTORTION IN BIS-INTERCALATED COMPLEXES
OverviewOverview
The bis-intercalators Flexi-Di and ditercalinium are synthetic dimers that, bis-intercalate into DNA and cause cell death in prokaryotes from futile, and abortive repair of DNA. Each is composed of two 7H-pyridocarbazole, units and a linker. Flexi-Di has a flexible spermine-like linker while, ditercalinium has a rigid bis(ethylpiperidinium) linker. This report, describing the 2.5-A X-ray structure of Flexi-Di complexed with, [d(BrCGCG)]2, appears to be the first report of a three-dimensional, structure of a DNA complex with a bis-intercalator with a flexible linker., DNA complex formation with a ditercalinium analog having a flexible linker, was not anticipated to yield unstacked and bent DNA as was observed in the, previously reported ditercalinium.[d(CGCG)]2 complex. Surprisingly, the, DNA in the Flexi-Di complex is bent to a degree exceeding that of the, ditercalinium complex. A comparison of the DNA complexes of Flexi-Di and, ditercalinium has allowed us to propose a mechanism by which these, bis-intercalators distort DNA. We propose that this class of, bis-intercalators pulls the internal base pairs into the major groove and, pushes the external base pairs into the minor groove. The result is a bend, toward the minor groove. It appears that hydrogen bonds between the linker, and the internal guanines effectively pull the central base pairs of the, complex out into the major groove. At the external regions of the complex, stacking interactions between the chromophores and terminal base pairs, effectively push the terminal base pairs into the minor groove. The result, of this push/pull combination is to bend the DNA.
About this StructureAbout this Structure
154D is a Protein complex structure of sequences from [1] with FLD as ligand. Full crystallographic information is available from OCA.
ReferenceReference
DNA distortion in bis-intercalated complexes., Peek ME, Lipscomb LA, Bertrand JA, Gao Q, Roques BP, Garbay-Jaureguiberry C, Williams LD, Biochemistry. 1994 Apr 5;33(13):3794-800. PMID:8142381
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