BIOINFORMATICS<-->STRUCTURE
Jerusalem, Israel, November 17-21, 1996

Abstract


The topology of nucleic acids with overhangs

Muttaiya Sundaralingam and Baocheng Pan

The Departments of Chemistry and Biochemistry, The Ohio State Biochemistry and Biophysics Programs, The Ohio State University, 1060 Carmack Road, Columbus, OH 43210, USA


The DNA heptamer d(GCGCGCG) has been solved at 1.65 Å resolution, with R value of 18.4% for 3598 reflections, including 286 DNA atoms, 2 cobalt hexamine complexes and 54 water molecules (Pan et al., 1996). The heptamer adopts the Z-DNA d(CGCGCG) structure with a 5'- G overhang instead of the A-DNA d(GCGCGC) with a 3'-G overhang. In contrast, the RNA structure r(UUCGCG) at 1.4 Å resolution formed an A- RNA, even though it has the left-handed sequence CGCG (Wahl et al., 1996). The third overhang crystal structure d(GCGAATTCG) formed a B- DNA with a 5'-G overhang (Meervelt et al., 1995). Theses three structures exhibit different topologies, A-, B- and Z-forms. The structure of all-alternating d(GCGCGCG) is left handed, while the semi-alternating r(UUCGCG) and d(GCGAATTCG) are right-handed. In all three cases, the structures have a 5' overhang instead of a 3' overhang, consistent with the previous biochemical (Williams et al., 1994) and biophysical studies (Senior et al., 1988). The 5'-G in the first structure is involved in a reverse Hoogsteen G.G pair on parallel strands, where both G's are in anti glycosidic conformation and C2'-endo puckering. The displacement of one of the G's relative to the other in the pair results in a bifurcated hydrogen bond and a CH...O interaction. The 5'-UU overhang in the second structure (r(UUCGCG)) forms a CH...O interaction that stabilizes the single CO...NH hydrogen bond in the novel U.U base pair. The 5'-G in the third structure (d(GCGAATTCG)) forms a base triplet (C.G)*G. It is clear that the overhang residues are more flexible and adopt novel conformations and base pairing. The details of the G.G and U.U base pairing in the 5'-overhang structures will be discussed.

References
Meervelt, L. V., Vleighe, D., Dautant, A., Gallois, B., Precigoux, G. & Kennard, O. (1995) Nature 374, 742-744.
Pan, B., Wahl, M. C., Ban, C & Sundaralingam, M. (1996) to be published.
Senior, M., Jones, R. A. & Breslauer, K. J. (1988) Biochemistry 27, 3879- 3885.
Wahl, M. C., Rao, S. T. & Sundaralingam, M. (1995) Nature Structural Biology 3, 24-31.
Williams, J. C., Case-Green, S. C., Mir, K. U. & Southern E. M. (1994) Nuc. Acids Res. 22, 1365-1367.

Research supported by NIH Grant GM17378.


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