Biostructural chemistry of magnesium. regulation of mithramycin-DNA interactions by Mg2+ coordination.
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.
Huang
H W
HW
Evans Laboratory of Chemistry, Ohio State University, Columbus 43210, USA.
Li
D
D
Cowan
J A
JA
D002413:Cations, Divalent; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004278:DNA, Superhelical / Q000737:chemistry / Q000378:metabolism; D008274:Magnesium / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009690:Nucleic Acid Conformation; D008926:Plicamycin / Q000737:chemistry / Q000378:metabolism*
D002413:Cations, Divalent; D004278:DNA, Superhelical; D004247:DNA; D008274:Magnesium; D008926:Plicamycin