Solution structure and hydration patterns of a Pyrimidine·Purine·Pyrimidine DNA triplex containing a novel T·CG base-triple

Abstract

The solution structure of a pyrimidine purine pyrimidine DNA triplex containing a novel T·CG base-triple has been determined via two and three-dimensional NMR spectroscopy and restrained molecular dynamics simulations incorporating explicit solvent and counter-ions. The T·CG triple, which expands the triplex code, is stabilized by a single hydrogen bond between the O-2 atom of thymine and the free amino proton of cytosine in the Watson-Crick C·G base-pair. This hydrogen bonding alignment produces large variations in helical twist at the dinucleotide steps involving the thymine residue. Localized structural perturbations in the purine-rich strand of the molecule are observed around the cytosine residue in the T·CG triple. Globally, the triplex resembles the solution structure of a previously solved pyrimidine-purine-pyrimidine DNA triplex containing an unusual G·TA triple. Also conserved are the sites and patterns of hydration in the two triplexes.