Role of Mg++ in the mithramycin-DNA interaction: evidence for two types of mithramycin-Mg++ complex.
Mithramycin(MTR, structure shown in Figure 1) [and the related compound Chromomycin A3(CHRA3)] are antitumor antibiotics which inhibit DNA dependent RNA polymerase activity via reversible interaction with DNA only in the presence of divalent metal ion such as Mg++. In order to understand the role of Mg++ in MTR-DNA interaction, absorbance and CD spectroscopic techniques are employed to study the binding of MTR to Mg++. These studies show: i) the drug alone binds to Mg++ and ii) two different types of drug-Mg++ complexes are formed at low(Complex I) and high(Complex II) ratios of the concentration of Mg++ and MTR. We propose that these two complexes would bind to the same DNA with different affinities and rates. This result suggests that the relative concentration of Mg++ is an important factor to be taken into account to understand the molecular basis of MTR-DNA interaction.
Aich
P
P
Crystallography & Molecular Biology Division, Saha Institute of Nuclear Physics, Calcutta, India.
Dasgupta
D
D
D002942:Circular Dichroism; D004247:DNA / Q000378:metabolism*; D007700:Kinetics; D008274:Magnesium / Q000378:metabolism*; D008926:Plicamycin / Q000378:metabolism*
D004247:DNA; D008274:Magnesium; D008926:Plicamycin