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  • Title: Biostructural chemistry of magnesium. regulation of mithramycin-DNA interactions by Mg2+ coordination.
    Author: Huang HW, Li D, Cowan JA.
    Journal: Biochimie; 1995; 77(9):729-38. PubMed ID: 8789464.
    Abstract:
    Divalent magnesium promotes the selective binding of mithramycin to a cognate DNA sequence (5'-XXGCXX-3') by a coupled mechanism requiring local conformational changes in the polynucleotide backbone and a structural rearrangement of the mithramycin dimer. Circular dichroism, 31P-NMR, and analysis of the topological change of supercoiled plasmid DNA by agarose gel electrophoresis support these conclusions and offer insight on the regulatory role of Mg2+. Molecular modeling suggests that sequence selectivity arises from preferential coordination of Mg2+ to d(GpC) domains in the minor groove of Z-type DNA. We suggest a specific structural role for the essential divalent magnesium ion, and propose a revision of the binding mechanism previously devised for the mithramycin/DNA complex. This revised structural model is entirely consistent with NMR results reported for the mithramycin and related chromomycin complexes, but previously interpreted in terms of an A-type configuration.
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