Conformational flexibility in single-stranded oligonucleotides: crystal structure of a hydrated calcium salt of adenylyl-(3'--5')-adenosine.

The crystal and molecular structure of a hydrated calcium salt of adenylyl-(3'--5')-adenosine(ApA) was determined from X-ray diffraction data collected on an automated diffractometer. Crystals of the salt are orthorhombic, space group P21212, with a = 30.614 (3), b = 17.894 (2), and c = 5.373 (1) A. The structure was solved by a combination of Patterson and direct methods and refined by least squares. The final value of the R index is 0.08. The 5'-terminal adenosine residue has a C(2')-endo ribose and assumes a syn conformation, which is stabilized by an O(5')-H...N(3) hydrogen bond within the nucleoside. The 3'-terminal nucleoside has a C(3')-endo ribose and is in the anti conformation. Both omega and omega', the torsion angles within the phosphodiester group, are approximately 60 degrees. Adenine bases from adjacent anions are joined by pairs of N(6)-H...N(1) hydrogen bonds and are stacked with symmetry-related bases. The calcium ion is bound to the dinucleoside phosphate by a direct interaction with the phosphate group and by outer-sphere, ligand-mediated interactions with O(2') of the 5'-terminal nucleoside and N(7) of the 3'-terminal nucleoside. This tridentate interaction of the ApA anion with the calcium coordination sphere probably enhances the stability of the observed ApA conformation. When combined with other crystallographic studies of ApA conformations, the crystal structure of this calcium salt provides additional evidence that dinucleoside phosphates have considerable conformational flexibility.