DSSR-enabled G4 identification/annotation: PDB entry 6zl9
Summary information and primary citation
- 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 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)
List of 3 G-tetrads
1 glyco-bond=---- sugar=---- groove=---- planarity=0.188 type=other O+ nts=4 GGGG A.DG18,A.DG22,A.DG27,A.DG31 2 glyco-bond=---- sugar=---- groove=---- planarity=0.227 type=other O+ nts=4 GGGG A.DG19,A.DG23,A.DG28,A.DG32 3 glyco-bond=---- sugar=---- groove=---- planarity=0.213 type=other O+ 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-tetrads, INTRA-molecular, with 1 stem
|
1 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG18,A.DG22,A.DG27,A.DG31 2 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG19,A.DG23,A.DG28,A.DG32 3 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ 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=--- sugar=--- nts=3 GGG A.DG18,A.DG19,A.DG20 strand#2 DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG22,A.DG23,A.DG24 strand#3 DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG27,A.DG28,A.DG29 strand#4 DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG31,A.DG32,A.DG33 |
| 2 stacking diagrams | |
|
1 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG18,A.DG22,A.DG27,A.DG31 |
|
2 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG19,A.DG23,A.DG28,A.DG32 |
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.DG18,A.DG22,A.DG27,A.DG31 2 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG19,A.DG23,A.DG28,A.DG32 3 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ 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=--- sugar=--- nts=3 GGG A.DG18,A.DG19,A.DG20 strand#2 U DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG22,A.DG23,A.DG24 strand#3 U DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG27,A.DG28,A.DG29 strand#4 U DNA glyco-bond=--- sugar=--- 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 |