Molecular structure of cyclic deoxydiadenylic acid at atomic resolution.

The molecular structure of a small cyclic nucleotide, cyclic deoxydiadenylic acid, has been determined by single-crystal X-ray diffraction analysis and refined to an R factor of 7.8% at 1.0-A resolution. The crystals are in the monoclinic space group C2 with unit cell dimensions of a = 24.511 (3) A, b = 24.785 (3) A, c = 13.743 (3) A, and beta = 94.02 (2) degrees. The structure was solved by the direct methods program SHELXS-86. There are 2 independent cyclic d(ApAp) molecules, 2 hydrated magnesium ions, and 26 water molecules in the asymmetric unit of the unit cell. The two cyclic d(ApAp) molecules have similar conformations within their 12-membered sugar-phosphate backbone ring, but they have quite different appearances due to the different glycosyl torsion angles that make one molecule more compact and the other extended and open. Three of the four deoxyribose rings are in the less common C3'-endo conformation. All four phosphate groups have their phosphodiester torsion angles alpha/zeta in the gauche(+)/gauche(+) conformation. One of the cyclic d(ApAp) molecules associates with another symmetry-related molecule to form a self-intercalated dimer that is a stable structure in solution, as observed in NMR studies. Many interesting intermolecular interactions, including base-base stacking, ribose-base stacking, base pairing, base-phosphate hydrogen bonding, and metal ion-phosphate interactions, are found in the crystal lattice. This structure may be relevant for understanding the conformational potentiality of an endogenous biological regulator of cellulose synthesis, cyclic (GpGp).