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Magnesium-nucleic acid conformational changes and cancer
Abstract:
The magnesium interaction with the mononucleotide guanosine-5'-monophosphate disodium salt (5'-GMP Na2 or G5'p) has been studied by Fourier transform infrared spectroscopy. The results have been compared with previously obtained proton nuclear magnetic data on the same system as well as other similar systems. The spectra here show that the natural conformation of the mononucleotide changes significantly in the presence of normal concentrations of magnesium chloride (approximately 10(-3) M) from the predominantly C2'-endo,anti into C3'-endo,anti conformation of the sugar ring, and the phosphate group becomes virtually gauche-gauche. The marker bands for C2'-endo,anti and C3'-endo,anti are shown near 820 cm-1 and 803 cm-1, respectively. The infrared spectroscopic results found here indicate that the unit Mg(H2O)2+5 is coordinated at the N7 site of the base guanine and hydrogen bonded via the water molecules to the carbonyl C6 = O and to the phosphate negative oxygens. This type of bonding is very similar to the binding of the antitumor drug cis-platinum, which is chemically (covalently) bound to the N7 site of guanine in the same molecule or in nucleic acids.
Insights
Magnesium ions alter the structure of guanosine-5'-monophosphate (5'-GMP Na2), shifting its sugar ring conformation. This magnesium binding at the N7 guanine site resembles cis-platinum
Area of Science:
- Biochemistry
- Molecular Biology
- Spectroscopy
Background:
- Guanosine-5 -monophosphate (5 -GMP Na2) is a fundamental nucleotide.
- Magnesium ions are crucial cofactors in numerous biological processes.
- Understanding nucleotide-metal interactions is key to deciphering biological mechanisms.
Purpose of the Study:
- To investigate the structural impact of magnesium ions on 5 -GMP Na2.
- To elucidate the binding site and mode of magnesium on 5 -GMP Na2.
- To compare magnesium binding with that of other metal ions, such as cis-platinum.
Main Methods:
- Fourier transform infrared (FTIR) spectroscopy was employed.
- Proton nuclear magnetic resonance (NMR) data were used for comparison.
- Analysis of marker bands (820 cm-1 and 803 cm-1) associated with sugar ring conformations.
Main Results:
- Magnesium ions induced a significant conformational change in the 5 -GMP Na2 sugar ring from C2 -endo,anti to C3 -endo,anti.
- The phosphate group adopted a gauche-gauche conformation.
- The Mg(H2O)2+5 complex coordinated to the N7 site of guanine, with water molecules forming hydrogen bonds to the C6=O and phosphate oxygens.
Conclusions:
- Magnesium binding significantly alters the conformation of 5 -GMP Na2.
- The observed binding mode at the N7 guanine site is analogous to that of cis-platinum.
- This study provides insights into nucleotide-metal interactions relevant to biological systems and drug binding.