Summary information

PDB id
7z9l
Class
DNA
Method
NMR
Summary
Phen-dc3 intercalation causes hybrid-to-antiparallel transformation of human telomeric DNA g-quadruplex
Reference
Ghosh A, Trajkovski M, Teulade-Fichou MP, Gabelica V, Plavec J (2022): "Phen-DC 3 Induces Refolding of Human Telomeric DNA into a Chair-Type Antiparallel G-Quadruplex through Ligand Intercalation." Angew.Chem.Int.Ed.Engl., 61, e202207384. doi: 10.1002/anie.202207384.
Abstract
Human telomeric G-quadruplex DNA structures are attractive anticancer drug targets, but the target's polymorphism complicates the drug design: different ligands prefer different folds, and very few complexes have been solved at high resolution. Here we report that Phen-DC3 , one of the most prominent G-quadruplex ligands in terms of high binding affinity and selectivity, causes dTAGGG(TTAGGG)3 to completely change its fold in KCl solution from a hybrid-1 to an antiparallel chair-type structure, wherein the ligand intercalates between a two-quartet unit and a pseudo-quartet, thereby ejecting one potassium ion. This unprecedented high-resolution NMR structure shows for the first time a true ligand intercalation into an intramolecular G-quadruplex.
G4 notes
3 G-tetrads, 1 G4 helix, 1 G4 stem, 3(+Ln+Lw+Ln), chair(2+2), UDUD

Base-block schematics in six views

PyMOL session file PDB file View in 3Dmol.js

List of 3 G-tetrads

 1 glyco-bond=s-s- sugar=3--- groove=wnwn planarity=0.227 type=other  nts=4 GGGG A.DG3,A.DG23,A.DG15,A.DG11
 2 glyco-bond=s-s- sugar=---- groove=wnwn planarity=0.227 type=other  nts=4 GGGG A.DG4,A.DG22,A.DG16,A.DG10
 3 glyco-bond=-s-s sugar=---- groove=wnwn planarity=0.176 type=other  nts=4 GGGG A.DG5,A.DG21,A.DG17,A.DG9

List of 1 G4-helix

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

 1  glyco-bond=s-s- sugar=3--- groove=wnwn Major-->WC nts=4 GGGG A.DG3,A.DG23,A.DG15,A.DG11
 2  glyco-bond=s-s- sugar=---- groove=wnwn Major-->WC nts=4 GGGG A.DG4,A.DG22,A.DG16,A.DG10
 3  glyco-bond=-s-s sugar=---- groove=wnwn WC-->Major nts=4 GGGG A.DG5,A.DG21,A.DG17,A.DG9
  step#1  mp(<<,backward) area=0.00  rise=6.67 twist=19.2
  step#2  mm(<>,outward)  area=19.99 rise=3.42 twist=15.2
  strand#1 DNA glyco-bond=ss- sugar=3-- nts=3 GGG A.DG3,A.DG4,A.DG5
  strand#2 DNA glyco-bond=--s sugar=--- nts=3 GGG A.DG23,A.DG22,A.DG21
  strand#3 DNA glyco-bond=ss- sugar=--- nts=3 GGG A.DG15,A.DG16,A.DG17
  strand#4 DNA glyco-bond=--s sugar=--- nts=3 GGG A.DG11,A.DG10,A.DG9

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2 stacking diagrams
 1  glyco-bond=s-s- sugar=3--- groove=wnwn Major-->WC nts=4 GGGG A.DG3,A.DG23,A.DG15,A.DG11
2 glyco-bond=s-s- sugar=---- groove=wnwn Major-->WC nts=4 GGGG A.DG4,A.DG22,A.DG16,A.DG10
step#1 mp(<<,backward) area=0.00 rise=6.67 twist=19.2

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 2  glyco-bond=s-s- sugar=---- groove=wnwn Major-->WC nts=4 GGGG A.DG4,A.DG22,A.DG16,A.DG10
3 glyco-bond=-s-s sugar=---- groove=wnwn WC-->Major nts=4 GGGG A.DG5,A.DG21,A.DG17,A.DG9
step#2 mm(<>,outward) area=19.99 rise=3.42 twist=15.2

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List of 1 G4-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.

Stem#1, 3 G-tetrad layers, 3 loops, INTRA-molecular, UDUD, anti-parallel, 3(+Ln+Lw+Ln), chair(2+2)

 1  glyco-bond=s-s- sugar=3--- groove=wnwn Major-->WC nts=4 GGGG A.DG3,A.DG23,A.DG15,A.DG11
 2  glyco-bond=s-s- sugar=---- groove=wnwn Major-->WC nts=4 GGGG A.DG4,A.DG22,A.DG16,A.DG10
 3  glyco-bond=-s-s sugar=---- groove=wnwn WC-->Major nts=4 GGGG A.DG5,A.DG21,A.DG17,A.DG9
  step#1  mp(<<,backward) area=0.00  rise=6.67 twist=19.2
  step#2  mm(<>,outward)  area=19.99 rise=3.42 twist=15.2
  strand#1  U DNA glyco-bond=ss- sugar=3-- nts=3 GGG A.DG3,A.DG4,A.DG5
  strand#2  D DNA glyco-bond=--s sugar=--- nts=3 GGG A.DG23,A.DG22,A.DG21
  strand#3  U DNA glyco-bond=ss- sugar=--- nts=3 GGG A.DG15,A.DG16,A.DG17
  strand#4  D DNA glyco-bond=--s sugar=--- nts=3 GGG A.DG11,A.DG10,A.DG9
  loop#1 type=lateral   strands=[#1,#4] nts=3 TTA A.DT6,A.DT7,A.DA8
  loop#2 type=lateral   strands=[#4,#3] nts=3 TTA A.DT12,A.DT13,A.DA14
  loop#3 type=lateral   strands=[#3,#2] nts=3 TTA A.DT18,A.DT19,A.DA20

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