5Z80

Solution structure for the 1:1 complex of a platinum(II)-based tripod bound to a hybrid-1 human telomeric G-quadruplex

Summary for 5Z80

• Entry DOI: 10.2210/pdb5z80/pdb
• NMR Information: BMRB: 36159
• Descriptor: G-quadruplex DNA (26-MER), 4-[1-(2,5,8-triazonia-1$l^4-platinabicyclo[3.3.0]octan-1-yl)pyridin-1-ium-4-yl]-N,N-bis[4-[1-(2,5,8-triazonia-1$l^4-platinabicyclo[3.3.0]octan-1-yl)pyridin-1-ium-4-yl]phenyl]aniline (2 entities in total)
• Functional Keywords: intramolecular g-quadruplex, human telomeric g-quadruplex, platinum(ii) complex, ligand-dna complex, dna
• Biological source: Homo sapiens
• Total number of polymer chains: 1
• Total formula weight: 9607.63

Authors

Liu, W.T.,Zhong, Y.F.,Liu, L.Y.,Zeng, W.J.,Wang, F.Y.,Yang, D.Z.,Mao, Z.W. (deposition date: 2018-01-30, release date: 2018-09-19, Last modification date: 2024-05-01)

Primary citation

Liu, W.,Zhong, Y.F.,Liu, L.Y.,Shen, C.T.,Zeng, W.,Wang, F.,Yang, D.,Mao, Z.W.
Solution structures of multiple G-quadruplex complexes induced by a platinum(II)-based tripod reveal dynamic binding
Nat Commun, 9:3496-3496, 2018

PubMed Abstract: 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.

PubMed: 30158518
DOI: 10.1038/s41467-018-05810-4

Experimental method

SOLUTION NMR