Journal of the American Chemical Society vol:122 issue:2 pages:232-240
An unprejudiced final model of the daunomycin-d(CGCGCG) complex was obtained at 1.1 Angstrom resolution and at 100K after unrestrained SHELXL refinement, which was possible thanks to the high data-to-parameter ratio and which provided us with true standard deviations on positions and distances. The structural pattern that emerges from the refinement proves that the sugar phosphate backbone is considerably more conformationally flexible than was previously observed [Biochemistry 1991, 30, 3812-3815; J. Biol. Chem. 1993, 268, 10095-10101]. All phosphates las well as one sugar moiety) that are not rigidified by intercalation of the drug molecule are found to adopt two or more distinct conformations. Furthermore, the high quality of the data enabled us to find double conformations for several waters associated with the flexible phosphates or with flexible groups of the daunomycin molecule. These present findings suggest that the crystal lattice still allows for a certain conformational freedom of the DNA in the crystal. This freedom refers to the multiple conformations observed in the group of final models resulting from an NMR structure determination.