Crystallographic studies of metal ion - DNA interactions: Different binding modes of cobalt(II), copper(II) and barium(II) to nof guanines in Z-DNA and a drug-DNA complex

Metal ion coordination to nucleic acids is not only required for charge neutralization, it is also essential for the biological function of nucleic acids. The structural impact of different metal ion coordinations on DNA helices is an open question. We carried out X-ray diffraction analyses of the interactions of the two transition metal Ions Co(ll) and Cu(ll) and an alkaline earth metal Ion Ba(ll), with DNA of different conformations. In crystals, Co(ll) Ion binds exclusively at the N⁷ position of guanine bases by direct coordination. The coordination geometry around Co(ll) is octahedral, although some sites have an incomplete hydration shell. The averaged Co-N⁷ bond distance is 2.3.A. The averaged Co-N⁷-C⁸ angle Is 121°, significantly smaller than the value of 128° If the Cc/N⁷ vector were to bisect the C⁵-N⁷-C⁸ bond angle. Model building of Co(ll) binding to guanine N⁷ In B/DNA indicates that the coordinated waters in the axial positions would have a van der Waals clash with the neighboring base on the 5' side. In contrast, the major groove of A-DNA does not have enough room to accommodate the entire hydration shell. This suggests that Co(ll) binding to either B-DNA or A-DNA may induce significant conformational changes. The Z-DNA structure of Cu(ll)-soaked CGCGTG crystal revealed that the Cu(ll) Ion is bis-coordinated to N⁷ position of G10 and 'G12 (denotes a symmetry-related position) bases with a trigonal blpyramld geometry, suggesting a possible N⁷-Cu-N⁷ crosslinking mechanism. A similar bis-coordination to two guanines has also been seen in the interaction of Ba(ll) in m'CGUAmSCG Z-DNA crystal and of Ba(ll) with two other Z-DNA crystals.