HYDRATION PATTERNS AND INTERMOLECULAR INTERACTIONS IN A-DNA CRYSTAL-STRUCTURES - IMPLICATIONS FOR DNA RECOGNITION

Crystallographic studies of DNA fragments of the A and B conformations have shown that the structure and hydration of the DNA double helix d epend both on the base sequence and on the environment. Detailed analy ses of solvent organization in DNA crystals and its role in intermolec ular interactions have been reported mainly for B-DNA structures. We h ave determined the crystal structures of several isomorphous A-DNA oct amers at resolutions from 1.8 to 2.5 Angstrom and refined them by the same procedure. Comparative analysis of five independently refined str uctures in terms of hydration and intermolecular interactions has been performed leading to the following findings. The A-DNA major groove i s extensively hydrated and together with the hydration shells of the s ugar-phosphate backbone can form an ordered network of fused polygons. The water structure of the phosphate backbone is less conserved than that of the grooves. Characteristic hydration patterns are associated with specific base sequences. The A-DNA minor groove provides sites fo r intermolecular contacts through hydrophobic and polar interactions. Well-ordered water molecules mediate interduplex interactions that inv olve either the grooves or the backbone, or both. The direct and water -mediated intermolecular interactions observed in the A-DNA crystal st ructures are relevant to various recognition motifs between DNA and ot her molecules. In particular, intermolecular interactions at the DNA m inor groove are analogous to those observed in the recently reported c rystal structures of complexes between the TATA-binding protein and th e TATA-box.