5Z80

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


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 10 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


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Literature

Solution structures of multiple G-quadruplex complexes induced by a platinum(II)-based tripod reveal dynamic binding

Liu, W.Zhong, Y.F.Liu, L.Y.Shen, C.T.Zeng, W.Wang, F.Yang, D.Mao, Z.W.

(2018) Nat Commun 9: 3496-3496

  • DOI: https://doi.org/10.1038/s41467-018-05810-4
  • Primary Citation of Related Structures:  
    5Z80, 5Z8F

  • 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.


  • Organizational Affiliation

    MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275, China.


Macromolecules
Find similar nucleic acids by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains LengthOrganismImage
G-quadruplex DNA (26-MER)26Homo sapiens
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
9F0 (Subject of Investigation/LOI)
Query on 9F0

Download Ideal Coordinates CCD File 
B [auth A]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
C45 H63 N13 Pt3
HWOQXVGDGHJZJY-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 10 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
973 programChina2014CB845604 and 2015CB856301
National Science Foundation of ChinaChina21231007 and 21572282
Ministry of Education of ChinaChinaIRT-17R111
Science and Technology Planning Project of Guangdong ProvinceChina2013B051000047 and 207999

Revision History  (Full details and data files)

  • Version 1.0: 2018-09-19
    Type: Initial release