2MB3

Solution structure of an intramolecular (3+1) human telomeric G-quadruplex bound to a telomestatin derivative

Experimental Data Snapshot

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

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This is version 1.3 of the entry. See complete history. 


Literature

Solution structure of an intramolecular (3 + 1) human telomeric g-quadruplex bound to a telomestatin derivative.

Chung, W.J., Heddi, B., Tera, M., Iida, K., Nagasawa, K., Phan, A.T.

(2013) J Am Chem Soc 135: 13495-13501

  • DOI: https://doi.org/10.1021/ja405843r
  • Primary Citation of Related Structures:  
    2MB3

  • PubMed Abstract: 

    Guanine-rich human telomeric DNA can adopt secondary structures known as G-quadruplexes, which can be targeted by small molecules to achieve anticancer effects. So far, the structural information on complexes between human telomeric DNA and ligands is limited to the parallel G-quadruplex conformation, despite the high structural polymorphism of human telomeric G-quadruplexes. No structure has been yet resolved for the complex with telomestatin, one of the most promising G-quadruplex-targeting anticancer drug candidates. Here we present the first high-resolution structure of the complex between an intramolecular (3 + 1) human telomeric G-quadruplex and a telomestatin derivative, the macrocyclic hexaoxazole L2H2-6M(2)OTD. This compound is observed to interact with the G-quadruplex through π-stacking and electrostatic interactions. This structural information provides a platform for the design of topology-specific G-quadruplex-targeting compounds and is valuable for the development of new potent anticancer drugs.

    • Organizational Affiliation: 

    School of Physical and Mathematical Sciences, Nanyang Technological University , Singapore.


Macromolecules

Find similar nucleic acids by:  Sequence   |   3D Structure  

Entity ID: 1
MoleculeChains LengthOrganismImage
DNA_(5'-D(*TP*TP*GP*GP*GP*TP*TP*AP*GP*GP*GP*TP*TP*AP*GP*GP*GP*TP*TP*AP*GP*GP*GP*A)-3')24N/A
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
L2H
Query on L2H
Download Ideal Coordinates CCD File 
B [auth A](12S,27S)-12,27-bis(4-aminobutyl)-4,30-dimethyl-3,7,14,18,22,29-hexaoxa-11,26,31,32,33,34,35,36-octaazaheptacyclo[26.2. 1.1~2,5~.1~6,9~.1~13,16~.1~17,20~.1~21,24~]hexatriaconta-1(30),2(36),4,6(35),8,13(34),15,17(33),19,21(32),23,28(31)-dode caene-10,25-dione
C32 H34 N10 O8
VFOYOVBIUSPROZ-ROUUACIJSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
L2H PDBBind:  2MB3 IC50: 7400 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

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

Structure Validation

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View more in-depth experimental data
Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-08-28
    Type: Initial release
  • Version 1.1: 2013-09-25
    Changes: Database references
  • Version 1.2: 2023-06-14
    Changes: Data collection, Database references, Derived calculations, Other, Structure summary
  • Version 1.3: 2024-05-15
    Changes: Data collection, Database references