Theoretical analyses on the role of Mg2+ ions in ribozyme reactions

To elucidate the role of the Mg2+ ion in ribozyme reactions, we carried out ab initio molecular orbital investigations on dianionic trimethoxyphosphorane A and its Mg2+ complex (overall a neutral molecule) as a model system for the reaction center of Tetrahymena-type ribozyme. Although dianionic oxyphosphorane A concentrates its negative charges on the equatorial phosphoryl oxygens, the coordination of the Mg2+ ion between these two oxygens is unlikely. Geometry optimizations of the complex and the electrostatic potential of A both suggest that Mg2+ coordination preferably occurs in the region between the axial oxygen and the equatorial phosphoryl oxygen. The considerations of electrostatic potential rationalize the geometries of carboxylate-metal and phosphate-metal interactions extracted from the Cambridge Structural Database as well. Consequently, the Mg2+ ion at the active site of Tetrahymena-type ribozyme most likely lies in the regions between the axial and equatorial oxygens. The axial-equatorial coordinations of Mg2+ ions conceivably increase the electronegativities of the axial oxygens and facilitate cleavage of the phosphodiester bond located at the junction of the intron and the exon. It is thus likely that the Mg2+ ions play the key role in the phosphodiester cleavage reactions mediated by ribozymes.