Pluramycin and Protein-DNA Complexes
With both cisplatin and Et 743, drug and protein binding take place on opposite sides of
the DNA helix. This is in accordance with complementary shape recognition of DNA by
each pair of drug–protein complexes. The pluramycins, which have both major and
minor groove substituents linked by an intercalating chromophore, are structurally more
complex than drugs such as cisplatin and Et 743 because they "thread" the DNA helix.
Thus, trapping of either major or minor groove binding proteins by complementary shape
recognition in an analogous way to Et 743 or cisplatin is not possible. However, DNA
alkylation by pluramycin, at a specific site downstream of the TATA box, is enhanced
when TATA binding protein (TBP) is present. This DNA alkylation then results in TBP
being trapped at the TATA box (Fig. 2f) (Hansen & Hurley, 1996). These cooperative
interactions mediated at adjacent sites on DNA lead to the intriguing possibility of
disruption of transcription events with specificities that are much greater than anticipated,
based purely on the sequence specificity of the drug alone.
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