DSSR-derived G-quadruplex features in PDB entry 5z80
Citation: before a paper dedicated to the DSSR-G4 module comes out, please cite the 2015 DSSR paper published in Nucleic Acids Research.
- Solution structure for the 1:1 complex of a platinum(ii)-based tripod bound to a hybrid-1 human telomeric G-quadruplex
- Liu, W., Zhong, Y.F., Liu, L.Y., Shen, C.T., Zeng, W., Wang, F., Yang, D., Mao, Z.W.: (2018) "Solution structures of multiple G-quadruplex complexes induced by a platinum(II)-based tripod reveal dynamic binding." Nat Commun, 9, 3496-3496.
- DNA G-quadruplexes are not only attractive drug targets for cancer therapeutics, but also have important applications in supramolecular assembly. Here, we report a platinum(II)-based tripod (Pt-tripod) specifically binds the biological relevant hybrid-1 human telomeric G-quadruplex (Tel26), and strongly inhibits telomerase activity. Further investigations illustrate Pt-tripod induces the formation of monomeric and multimeric Pt-tripod‒Tel26 complex structures in solution. We solve the 1:1 and the unique dimeric 4:2 Pt-tripod-Tel26 complex structures by NMR. The structures indicate preferential binding of Pt-tripod to the 5'-end of Tel26 at a low Pt-tripod/Tel26 ratio of 0-1.0. After adding more Pt-tripod, the Pt-tripod binds the 3'-end of Tel26, unexpectedly inducing a unique dimeric 4:2 structure interlocked by an A:A non-canonical pair at the 3'-end. Our structures provide a structural basis for understanding the dynamic binding of small molecules with G-quadruplex and DNA damage mechanisms, and insights into the recognition and assembly of higher-order G-quadruplexes.
- G4 notes
- 3 G-tetrads, 1 G4 helix, 1 G4 stem · 3(+P+Lw+Ln), (3+1), UUDU
1 glyco-bond=-s-s groove=wnwn planarity=0.357 type=other nts=4 GGGG A.DG4,A.DG22,A.DG18,A.DG10 2 glyco-bond=--s- groove=-wn- planarity=0.255 type=other nts=4 GGGG A.DG5,A.DG11,A.DG17,A.DG23 3 glyco-bond=--.- groove=-..- planarity=0.250 type=other nts=4 GGGG A.DG6,A.DG12,A.DG16,A.DG24
In DSSR, a G4-helix is defined by stacking interactions of G-tetrads, regardless of backbone connectivity, and may contain more than one G4-stem.
Helix#1, 3 G-tetrad layers, INTRA-molecular, with 1 stem
In DSSR, a G4-stem is defined as a G4-helix with backbone connectivity. Bulges are also allowed along each of the four strands.