| This thesis describes the use of nuclear magnetic resonance techniques to study the structure and dynamics of biological macromolecules in solution. Analysis of two-dimensional homonuclear spectra and complete relaxation matrix methods have been used to solve the high-resolution structure of an eleven base-pair DNA duplex that contains the consensus sequence for promoters recognized by sigmaK RNA polymerase, and two modified ten base-pair DNA-RNA duplexes: [Rp]- and [Sp]-phosphorothioated hybrid duplexes, that have the proR or the proS oxygen atom of all the backbone phosphate groups in the DNA strand replaced by a sulfur, respectively. Studying the structure of phophorothioated hybrid duplexes is important to understand the mode of action of antisense inhibitors. On the other hand, multidimensional heteronuclear NMR techniques have provided the experimental information to refine the structure of a 47 amino acid fragment of the Tva receptor extracellular domain that is used by avian leucosis and sarcoma viruses to target host cells. Furthermore, every one of these molecules has clearly shown evidence of flexibility that I further investigated by taking advantage of the NMR capabilities. This is particularly important to provide a complete description of biological macromolecules in solution that is critical to fully understand their function. |
