2E4I

Human Telomeric DNA mixed-parallel/antiparallel quadruplex under Physiological Ionic Conditions Stabilized by Proper Incorporation of 8-Bromoguanosines

Summary for 2E4I

• Entry DOI: 10.2210/pdb2e4i/pdb
• Descriptor: DNA (5'-D(*DAP*(BGM)P*DGP*DGP*DTP*DTP*DAP*(BGM)P*DGP*DGP*DTP*DTP*DAP*(BGM)P*(BGM)P*DGP*DTP*DTP*DAP*(BGM)P*DGP*DG)-3') (1 entity in total)
• Functional Keywords: telomere, quadruplex, mixed-parallel/antiparallel, dna
• Total number of polymer chains: 1
• Total formula weight: 7377.98

Authors

Matsugami, A.,Xu, Y.,Noguchi, Y.,Sugiyama, H.,Katahira, M. (deposition date: 2006-12-11, release date: 2007-12-11, Last modification date: 2024-05-29)

Primary citation

Matsugami, A.,Xu, Y.,Noguchi, Y.,Sugiyama, H.,Katahira, M.
Structure of a human telomeric DNA sequence stabilized by 8-bromoguanosine substitutions, as determined by NMR in a K+ solution
Febs J., 274:3545-3556, 2007

PubMed Abstract: The structure of human telomeric DNA is controversial; it depends upon the sequence contexts and the methodologies used to determine it. The solution structure in the presence of K(+) is particularly interesting, but the structure is yet to be elucidated, due to possible conformational heterogeneity. Here, a unique strategy is applied to stabilize one such structure in a K(+) solution by substituting guanosines with 8-bromoguanosines at proper positions. The resulting spectra are cleaner and led to determination of the structure at a high atomic resolution. This demonstrates that the application of 8-bromoguanosine is a powerful tool to overcome the difficulty of nucleic acid structure determination arising from conformational heterogeneity. The obtained structure is a mixed-parallel/antiparallel quadruplex. The structure of telomeric DNA was recently reported in another study, in which stabilization was brought about by mutation and resultant additional interactions [Luu KN, Phan AT, Kuryavyi V, Lacroix L & Patel DJ (2006) Structure of the human telomere in K(+) solution: an intramolecular (3+1) G-quadruplex scaffold. J Am Chem Soc 128, 9963-9970]. The structure of the guanine tracts was similar between the two. However, a difference was seen for loops connecting guanine tracts, which may play a role in the higher order arrangement of telomeres. Our structure can be utilized to design a small molecule which stabilizes the quadruplex. This type of molecule is supposed to inhibit a telomerase and thus is expected to be a candidate anticancer drug.

PubMed: 17561958
DOI: 10.1111/j.1742-4658.2007.05881.x

Experimental method

SOLUTION NMR