SOLUTION STRUCTURE OF A NON-PALINDROMIC 16 BASE-PAIR DNA RELATED TO THE HIV-1 KAPPA-B SITE - EVIDENCE FOR BI-BII EQUILIBRIUM INDUCING A GLOBAL DYNAMIC CURVATURE OF THE DUPLEX

H-1 and P-31 NMR spectroscopy have been used together with molecular m odelling to determine the fine structure of a non-palindromic 16 bp DN A containing the NF-kappa B binding site. Much emphasis has been place d upon NMR optimization of both two-dimensional P-31 NMR techniques to extract structural information defining the phosphodiester backbone c on formation and selective homonuclear 2D COSY experiments to determin e sugar conformations. NMR data show evidence for a dynamic behaviour of steps flanking the ten base-pairs of the NF-kappa B binding site. A BI-BII equilibrium at these steps is demonstrated and two models for each extreme conformation are proposed in agreement with NMR data. Ln the refined BII structures, the NF-kappa B binding site exhibits an in trinsic curvature towards the major groove that is magnified by the fo ur flanking steps in the BII conformation. Furthermore, the base-pairs are translated into the major groove. Thus, we present a novel mode o f dynamic intrinsic curvature compatible with the DNA curvature observ ed in the X-ray structure of the p50-DNA complex. (C) 1998 Academic Pr ess Limited.