Title
Binding of resveratrol to the minor groove of DNA sequences with AATT and TTAA segments induces differential stability
Author
Maya S. Nair, Samar D'Mello, Rashmi Pant, Krishna Mohan Poluri
Year
2017
Journal
Journal of Photochemistry and Photobiology B: Biology
Abstract
Interactions of a natural stilbene compound, resveratrol with two DNA sequences containing AATT/TTAA segments have been studied. Resveratrol is found to interact with both the sequences. The mode of interaction has been studied using absorption, steady state fluorescence and circular dichroism spectroscopic techniques. UV–visible absorption and fluorescence studies provided the information regarding the binding constants and the stoichiometry of binding, whereas circular dichroism studies depicted the structural changes in DNA upon resveratrol binding. Our results evidenced that, though resveratrol showed similar affinity to both the sequences, the mode of interactions was different. The binding constants of resveratrol to AATT/TTAA sequences were found to be 7.55 × 105 M− 1 and 5.42 × 105 M− 1 respectively. Spectroscopic data evidenced for a groove binding interaction. Melting studies showed that the binding of resveratrol induces differential stability to the DNA sequences d(CGTTAACG)2 and d(CGAATTCG)2. Fluorescence data showed a stoichiometry of 1:1 for d(CGAATTCG)2-resveratrol complex and 1:4 for d(CGTTAACG)2-resveratrol complex. Molecular docking studies demonstrated that resveratrol binds to the minor groove region of both the sequences to form stable complexes with varied atomic contacts to the DNA bases or backbone. Both the complexes are stabilized by hydrogen bond formation. Our results evidenced that modulation of DNA sequence within the same bases can greatly alter the binding geometry and stability of the complex upon binding to small molecule inhibitor compounds like resveratrol.
Instrument
J-1500
Keywords
Circular dichroism, DNA structure, Ligand binding, Thermal stability, Thermodynamics, Biochemistry