Metal-mediated base pairs expand the repertoire of nucleic acid structures and dynamics. Here we report solution structures and dynamics of duplex DNA containing two all-natural C-Hg-T metallo base pairs separated by six canonical base pairs. NMR experiments reveal a 3:1 ratio of well-resolved structures in dynamic equilibrium. The major species contains two (N3)T-Hg-(N3)C base pairs in a predominantly B-form helix. The minor species contains (N3)T-Hg-(N4)C base pairs and greater A-form characteristics. Ten-fold different J coupling constants (N,Hg) are observed for (N3)C-Hg (114 Hz) versus (N4)C-Hg (1052 Hz) connectivities, reflecting differences in cytosine ionization and metal-bonding strengths. Dynamic interconversion between the two types of C-Hg-T base pairs are coupled to a global conformational exchange between the helices. These observations inspired the design of a repetitive DNA sequence capable of undergoing a global B-to-A-form helical transition upon adding Hg, demonstrating that C-Hg-T has unique switching potential in DNA-based materials and devices.
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| http://dx.doi.org/10.1038/s41467-019-12440-x | DOI Listing |
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