Sequence selective coordination of Mg2+(aq) to DNA

Area of Science:

• Biophysical Chemistry
• Molecular Biology
• Nuclear Magnetic Resonance Spectroscopy

Background:

• Magnesium ions (Mg2+) are essential for DNA structure and function.
• Understanding the thermodynamics of magnesium-DNA interactions is crucial for various biological processes.
• Previous studies have suggested sequence-dependent binding, but quantitative thermodynamic data were limited.

Purpose of the Study:

• To quantify the thermodynamic parameters of magnesium binding to DNA sequences with varying guanine-cytosine (G/C) and adenine-thymine (A/T) content.
• To compare the binding affinities of Mg2+(aq) to G/C-rich DNA versus A/T-rich DNA.
• To investigate the coordination environment and dynamics of bound magnesium ions.

Main Methods:

• 25Mg Nuclear Magnetic Resonance (NMR) spectroscopy was employed to study magnesium binding.
• Variable temperature experiments were conducted to determine activation free energies and exchange rates.
• Quadrupole coupling constants were analyzed to infer the coordination state of magnesium.

Main Results:

• G/C-rich DNA demonstrated significantly higher binding affinity for Mg2+(aq) compared to A/T-rich DNA, up to 40-100 fold stronger.
• The coordination of Mg2+(aq) to G/C-DNA was found to be approximately 2.1-2.7 kcal (mole Mg2+)-1 more stable than to A/T-DNA.
• Analysis of quadrupole coupling constants indicated outer-sphere coordination of the magnesium hexahydrate ion, Mg(H2O)6(2+).

Conclusions:

• DNA sequence composition, specifically the G/C content, plays a critical role in determining magnesium ion binding affinity.
• The enhanced stability of magnesium binding to G/C-DNA has implications for DNA structural integrity and protein-DNA interactions.
• The findings provide quantitative thermodynamic insights into sequence-specific ion-DNA interactions.