5LIG

G-Quadruplex formed at the 5'-end of NHEIII_1 Element in human c-MYC promoter bound to triangulenium based fluorescence probe DAOTA-M2

Summary for 5LIG

• Entry DOI: 10.2210/pdb5lig/pdb
• NMR Information: BMRB: 34025
• Descriptor: DNA (5'-D(*TP*AP*GP*GP*GP*AP*GP*GP*GP*TP*AP*GP*GP*GP*AP*GP*GP*GP*T)-3'), 8,12-bis(2-morpholinoethyl)-8H-benzo[ij]xantheno[1,9,8-cdef][2,7]naphthyridin-12-iumhexafluorophosphate (2 entities in total)
• Functional Keywords: dna, g-quadruplex, c-myc promoter, ligand, daota-m2
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 7092.17

Authors

Kotar, A.,Wang, B.,Shivalingam, A.,Gonzalez-Garcia, J.,Vilar, R.,Plavec, J. (deposition date: 2016-07-14, release date: 2016-09-14, Last modification date: 2024-05-15)

Primary citation

Kotar, A.,Wang, B.,Shivalingam, A.,Gonzalez-Garcia, J.,Vilar, R.,Plavec, J.
NMR Structure of a Triangulenium-Based Long-Lived Fluorescence Probe Bound to a G-Quadruplex.
Angew.Chem.Int.Ed.Engl., 55:12508-12511, 2016

PubMed Abstract: An NMR structural study of the interaction between a small-molecule optical probe (DAOTA-M2) and a G-quadruplex from the promoter region of the c-myc oncogene revealed that they interact at 1:2 binding stoichiometry. NMR-restrained structural calculations show that binding of DAOTA-M2 occurs mainly through π-π stacking between the polyaromatic core of the ligand and guanine residues of the outer G-quartets. Interestingly, the binding affinities of DAOTA-M2 differ by a factor of two for the outer G-quartets of the unimolecular parallel G-quadruplex under study. Unrestrained MD calculations indicate that DAOTA-M2 displays significant dynamic behavior when stacked on a G-quartet plane. These studies provide molecular guidelines for the design of triangulenium derivatives that can be used as optical probes for G-quadruplexes.

PubMed: 27577037
DOI: 10.1002/anie.201606877

Experimental method

SOLUTION NMR