Summary information

PDB id
6zl9
Class
DNA
Method
NMR
Summary
Structure of a parallel c-myc modified with 5' duplex stem-loop overhang
Reference
Vianney YM, Preckwinkel P, Mohr S, Weisz K (2020): "Quadruplex-Duplex Junction: A High-Affinity Binding Site for Indoloquinoline Ligands." Chemistry, 26, 16910-16922. doi: 10.1002/chem.202003540.
Abstract
A parallel quadruplex derived from the Myc promoter sequence was extended by a stem-loop duplex at either its 5'- or 3'-terminus to mimic a quadruplex-duplex (Q-D) junction as a potential genomic target. High-resolution structures of the hybrids demonstrate continuous stacking of the duplex on the quadruplex core without significant perturbations. An indoloquinoline ligand carrying an aminoalkyl sidechain was shown to bind the Q-D hybrids with a very high affinity in the order K a ~ 10 7 M -1 irrespective of the duplex location at the quadruplex 3'- or 5'-end. NMR chemical shift perturbations identified the tetrad face of the Q-D junction as specific binding site for the ligand. However, calorimetric analyses revealed significant differences in the thermodynamic profiles upon binding to hybrids with either a duplex extension at the quadruplex 3'- or 5'-terminus. A large enthalpic gain and considerable hydrophobic effects are accompanied by the binding of one ligand to the 3'-Q-D junction, whereas non-hydrophobic entropic contributions favor binding with formation of a 2:1 ligand-quadruplex complex in case of the 5'-Q-D hybrid.
G4 notes
3 G-tetrads, 1 G4 helix, 1 G4 stem, 3(-P-P-P), parallel(4+0), UUUU

Base-block schematics in six views

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List of 3 G-tetrads

 1 glyco-bond=---- groove=---- planarity=0.188 type=other  nts=4 GGGG A.DG18,A.DG22,A.DG27,A.DG31
 2 glyco-bond=---- groove=---- planarity=0.227 type=other  nts=4 GGGG A.DG19,A.DG23,A.DG28,A.DG32
 3 glyco-bond=---- groove=---- planarity=0.213 type=other  nts=4 GGGG A.DG20,A.DG24,A.DG29,A.DG33

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=---- groove=---- WC-->Major nts=4 GGGG A.DG18,A.DG22,A.DG27,A.DG31
 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG19,A.DG23,A.DG28,A.DG32
 3  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG20,A.DG24,A.DG29,A.DG33
  step#1  pm(>>,forward)  area=11.54 rise=3.39 twist=29.0
  step#2  pm(>>,forward)  area=13.83 rise=3.48 twist=24.8
  strand#1 DNA glyco-bond=--- nts=3 GGG A.DG18,A.DG19,A.DG20
  strand#2 DNA glyco-bond=--- nts=3 GGG A.DG22,A.DG23,A.DG24
  strand#3 DNA glyco-bond=--- nts=3 GGG A.DG27,A.DG28,A.DG29
  strand#4 DNA glyco-bond=--- nts=3 GGG A.DG31,A.DG32,A.DG33

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2 stacking diagrams
 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG18,A.DG22,A.DG27,A.DG31
2 glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG19,A.DG23,A.DG28,A.DG32
step#1 pm(>>,forward) area=11.54 rise=3.39 twist=29.0

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 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG19,A.DG23,A.DG28,A.DG32
3 glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG20,A.DG24,A.DG29,A.DG33
step#2 pm(>>,forward) area=13.83 rise=3.48 twist=24.8

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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, UUUU, parallel, 3(-P-P-P), parallel(4+0)

 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG18,A.DG22,A.DG27,A.DG31
 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG19,A.DG23,A.DG28,A.DG32
 3  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG20,A.DG24,A.DG29,A.DG33
  step#1  pm(>>,forward)  area=11.54 rise=3.39 twist=29.0
  step#2  pm(>>,forward)  area=13.83 rise=3.48 twist=24.8
  strand#1  U DNA glyco-bond=--- nts=3 GGG A.DG18,A.DG19,A.DG20
  strand#2  U DNA glyco-bond=--- nts=3 GGG A.DG22,A.DG23,A.DG24
  strand#3  U DNA glyco-bond=--- nts=3 GGG A.DG27,A.DG28,A.DG29
  strand#4  U DNA glyco-bond=--- nts=3 GGG A.DG31,A.DG32,A.DG33
  loop#1 type=propeller strands=[#1,#2] nts=1 T A.DT21
  loop#2 type=propeller strands=[#2,#3] nts=2 TA A.DT25,A.DA26
  loop#3 type=propeller strands=[#3,#4] nts=1 T A.DT30

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