Summary information and primary citation

PDB-id
6zl2
Class
DNA
Method
NMR
Summary
Structure of a parallel c-myc modified with 3' 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 side chain was shown to bind the Q-D hybrids with a very high affinity in the order K<sub>a</sub> ≈10<sub>7</sub>  m<sub>-1</sub> 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, UUUU, parallel, 4+0, 3(-P-P-P)

Cartoon-block schematics in six views (download the tarball)

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List of 3 G-tetrads

 1 glyco-bond=---- sugar=--.- groove=---- planarity=0.370 type=other  O+ nts=4 GGGG A.DG4,A.DG8,A.DG13,A.DG17
 2 glyco-bond=---- sugar=-... groove=---- planarity=0.283 type=other  O+ nts=4 GGGG A.DG5,A.DG9,A.DG14,A.DG18
 3 glyco-bond=---- sugar=---- groove=---- planarity=0.179 type=other  O+ nts=4 GGGG A.DG6,A.DG10,A.DG15,A.DG19

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-tetrads, INTRA-molecular, with 1 stem
 1  glyco-bond=---- sugar=--.- groove=---- WC-->Major O+ nts=4 GGGG A.DG4,A.DG8,A.DG13,A.DG17
 2  glyco-bond=---- sugar=-... groove=---- WC-->Major O+ nts=4 GGGG A.DG5,A.DG9,A.DG14,A.DG18
 3  glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG6,A.DG10,A.DG15,A.DG19
  step#1  pm(>>,forward)  area=15.73 rise=3.47 twist=25.9
  step#2  pm(>>,forward)  area=15.05 rise=3.41 twist=24.7
  strand#1 DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG4,A.DG5,A.DG6
  strand#2 DNA glyco-bond=--- sugar=-.- nts=3 GGG A.DG8,A.DG9,A.DG10
  strand#3 DNA glyco-bond=--- sugar=..- nts=3 GGG A.DG13,A.DG14,A.DG15
  strand#4 DNA glyco-bond=--- sugar=-.- nts=3 GGG A.DG17,A.DG18,A.DG19

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2 stacking diagrams 
 1  glyco-bond=---- sugar=--.- groove=---- WC-->Major O+ nts=4 GGGG A.DG4,A.DG8,A.DG13,A.DG17
 2  glyco-bond=---- sugar=-... groove=---- WC-->Major O+ nts=4 GGGG A.DG5,A.DG9,A.DG14,A.DG18
  step#1  pm(>>,forward)  area=15.73 rise=3.47 twist=25.9

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 2  glyco-bond=---- sugar=-... groove=---- WC-->Major O+ nts=4 GGGG A.DG5,A.DG9,A.DG14,A.DG18
 3  glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG6,A.DG10,A.DG15,A.DG19
  step#2  pm(>>,forward)  area=15.05 rise=3.41 twist=24.7

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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-tetrads, 3 loops, INTRA-molecular, UUUU, parallel, 4+0, 3(-P-P-P)
 1  glyco-bond=---- sugar=--.- groove=---- WC-->Major O+ nts=4 GGGG A.DG4,A.DG8,A.DG13,A.DG17
 2  glyco-bond=---- sugar=-... groove=---- WC-->Major O+ nts=4 GGGG A.DG5,A.DG9,A.DG14,A.DG18
 3  glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG6,A.DG10,A.DG15,A.DG19
  step#1  pm(>>,forward)  area=15.73 rise=3.47 twist=25.9
  step#2  pm(>>,forward)  area=15.05 rise=3.41 twist=24.7
  strand#1  U DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG4,A.DG5,A.DG6
  strand#2  U DNA glyco-bond=--- sugar=-.- nts=3 GGG A.DG8,A.DG9,A.DG10
  strand#3  U DNA glyco-bond=--- sugar=..- nts=3 GGG A.DG13,A.DG14,A.DG15
  strand#4  U DNA glyco-bond=--- sugar=-.- nts=3 GGG A.DG17,A.DG18,A.DG19
  loop#1 type=propeller strands=[#1,#2] nts=1 T A.DT7
  loop#2 type=propeller strands=[#2,#3] nts=2 TA A.DT11,A.DA12
  loop#3 type=propeller strands=[#3,#4] nts=1 T A.DT16

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