STRUCTURE OF A NEW CRYSTAL FORM OF A DNA DODECAMER CONTAINING T-CENTER-DOT(O(6)ME)G BASE-PAIRS

The structure of the synthetic dodecamer {d[CGTGAATTC(O(6)Me)GCG]}(2) has been determined to a resolution of 2.25 Angstrom and refined to a final R factor of 16.7%. The volume of the unit cell is significantly smaller by 16% than the original Drew and Dickerson parent dodecamer [ Drew, H.R., Wing, R.M., Takano, T., Broka, C., Tanaka, S., Itakura, K. , & Dickerson, R.E. (1981) Proc. Natl. Acad. Sci. U.S.A. 78, 7318-7322 ]. The double helix is in a different position in the unit cell, rotat ed by -85.9 degrees, and translated by 9.9 Angstrom around the helical axis with respect to the parent structure. The intermolecular arrange ment of helices, characterized by double hydrogen bonded guanine-guani ne minor groove interactions, remains conserved. The molecular geometr y exhibits several significant changes that are related to the changed position of the helix and the presence of two mismatched base pairs w ith O-6-methylguanine. Both mispairs are found in a symmetrical T(anti ).(O(6)Me)G(anti) conformation, and the methyl groups are in proximal orientation. The hydration pattern of the structure is different and c an be related to changes in the minor groove geometry. An incorrect mo del that was isomorphous to the parent dodecamer could be refined to a low R factor. Characteristics of the refinement and of the geometry t hat are indicative of incorrect structures have been analyzed.