Structural Basis for Stabilization of Z-DNA by Cobalt Hexaammine and Magnesium Cations

In the equilibrium between B-DNA and Z-DNA in poly(dC-dG), the [Co(NH₃)₆]³⁺ ion stabilizes the Z form 4 orders of magnitude more effectively than the Mg²⁺ ion. The structural basis of this difference is revealed in Z-DNA crystal structures of d(CpGpCpGpCpG) stabilized by either Na⁺/Mg²⁺ or Na⁺/Mg²⁺ plus [Co(NH₃)₆]³⁺. The crystals diffract X-rays to high resolution, and the structures were refined at 1.25 A. The [Co(NH₃)₆]³⁺ ion forms five hydrogen bonds onto the surface of Z-DNA, bonding to a guanine O6 and N7 as well as to a phosphate group in the Zn conformation. The Mg²⁺ ion binds through its hydration shell with up to three hydrogen bonds to guanine N7 and O6. Higher charge, specific fitting of more hydrogen bonds, and a more stable complex all contribute to the great effectiveness of [Co(NH₃)₆]³⁺ in stabilizing Z-DNA.