Hexahydrated magnesium ions bind in the deep major groove and at the outermouth of A-form nucleic acid duplexes

Magnesium ions play important roles in the structure and function of nuclei c acids, Whereas the tertiary folding of RNA often requires magnesium ions binding to tight places where phosphates are clustered, the molecular basis of the interactions of magnesium ions with RNA helical regions is less wel l understood. We have refined the crystal structures of four decamer oligon ucleotides, d(ACCGGCCGGT), r(GCG)d(TATACGC), r(GC)d(GTATACGC) and r(G)d(GCG TATACGC) with bound hexahydrated magnesium ions at high resolution. The str uctures reveal that A-form nucleic acid has characteristic [Mg(H2O)(6)](2+) binding modes. One mode has the ion binding in the deep major groove of a GpN step at the O6/N7 sites of guanine bases via hydrogen bonds, Our crysta llographic observations are consistent with the recent NMR observations tha t in solution [Co(NH3)(6)](3+), a model ion of [Mg(H2O)(6)](2+), binds in a n identical manner, The other mode involves the binding of the ion to phosp hates, bridging across the outer mouth of the narrow major groove. These [M g(H2O)(6)](2+) ions are found at the most negative electrostatic potential regions of A-form duplexes. We propose that these two binding modes are imp ortant in the global charge neutralization, and therefore stability, of A-f orm duplexes.