Metal ions and the stereochemistry of ribozyme reactions

Inversion of configuration at phosphorus during ribozyme-catalyzed cleavage of RNA is usually considered unequivocal proof of in-line attack, but the relevant pseudorotation diagram for formation of the 2′,3′-cyclic phosphate shows that inversion is not inconsistent with adjacent attack as long as breakdown of the trigonal bipyramid is in-line. For the reaction to occur by adjacent attack, a normally unstable apical oxyanion in the trigonal bipyramidal intermediate would have to be stabilized. Density-functional calculations show that a metal ion such as magnesium could perform this stabilization. We conclude that the possibility of adjacent attack should not be too hastily dismissed in cases where the setup is closer to adjacent than to in-line geometry.