DSSR-enabled G4 identification/annotation: PDB entry 7pne
Summary information and primary citation
- PDB-id
- 7pne
- Class
- DNA
- Method
- NMR
- Summary
- Parallel q-d hybrid with 3' duplex stem-loop as a lateral snapback loop
- Reference
- Vianney YM, Weisz K (2022): "Indoloquinoline Ligands Favor Intercalation at Quadruplex-Duplex Interfaces." Chemistry, 28, e202103718. doi: 10.1002/chem.202103718.
- Abstract
- Quadruplex-duplex (Q-D) junctions are increasingly considered promising targets for medicinal and technological applications. Here, a Q-D hybrid with a hairpin-type snapback loop coaxially stacked onto the quadruplex 3'-outer tetrad was designed and employed as a target structure for the indoloquinoline ligand SYUIQ-5. NMR spectral analysis demonstrated high-affinity binding of the ligand at the quadruplex-duplex interface with association constants determined by isothermal titration calorimetry of about 10<sub>7</sub> M<sub>-1</sub> and large exothermicities ΔH° of -14 kcal/mol in a 120 mM K<sub>+</sub> buffer at 40 °C. Determination of the ligand-bound hybrid structure revealed intercalation of SYUIQ-5 between 3'-outer tetrad and the neighboring CG base pair, maximizing π-π stacking as well as electrostatic interactions with guanine carbonyl groups in close vicinity to the positively charged protonated quinoline nitrogen of the tetracyclic indoloquinoline. Exhibiting considerable flexibility, the SYUIQ-5 sidechain resides in the duplex minor groove. Based on comparative binding studies with the non-substituted N5-methylated indoloquinoline cryptolepine, the sidechain is suggested to confer additional affinity and to fix the alignment of the intercalated indoloquinoline aromatic core. However, selectivity for the Q-D junction mostly relies on the geometry and charge distribution of the indoloquinoline ring system. The presented results are expected to provide valuable guidelines for the design of ligands specifically targeting Q-D interfaces.
- G4 notes
- 3 G-tetrads, 1 G4 helix, 1 G4 stem, UUUU, parallel, 4+0, 2(-P-P-P)
Cartoon-block schematics in six views (download the tarball)
List of 3 G-tetrads
1 glyco-bond=---- sugar=---- groove=---- planarity=0.347 type=other O+ nts=4 GGGG A.DG4,A.DG7,A.DG12,A.DG16 2 glyco-bond=---- sugar=--.- groove=---- planarity=0.349 type=saddle O+ nts=4 GGGG A.DG5,A.DG8,A.DG13,A.DG17 3 glyco-bond=---s sugar=---- groove=--wn planarity=0.281 type=other O+ nts=4 GGGG A.DG9,A.DG14,A.DG18,A.DG36
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.DG7,A.DG12,A.DG16 2 glyco-bond=---- sugar=--.- groove=---- WC-->Major O+ nts=4 GGGG A.DG5,A.DG8,A.DG13,A.DG17 3 glyco-bond=s--- sugar=---- groove=n--w WC-->Major O+ nts=4 GGGG A.DG36,A.DG9,A.DG14,A.DG18 step#1 pm(>>,forward) area=13.50 rise=3.43 twist=26.8 step#2 pm(>>,forward) area=11.20 rise=3.47 twist=29.9 strand#1 DNA glyco-bond=--s sugar=--- nts=3 GGG A.DG4,A.DG5,A.DG36 strand#2 DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG7,A.DG8,A.DG9 strand#3 DNA glyco-bond=--- sugar=-.- nts=3 GGG A.DG12,A.DG13,A.DG14 strand#4 DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG16,A.DG17,A.DG18 |
| 2 stacking diagrams | |
|
1 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG4,A.DG7,A.DG12,A.DG16 |
|
2 glyco-bond=---- sugar=--.- groove=---- WC-->Major O+ nts=4 GGGG A.DG5,A.DG8,A.DG13,A.DG17 |
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, 2 G-tetrads, 3 loops, INTRA-molecular, UUUU, parallel, 4+0, 2(-P-P-P)
|
1 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG4,A.DG7,A.DG12,A.DG16 2 glyco-bond=---- sugar=--.- groove=---- WC-->Major O+ nts=4 GGGG A.DG5,A.DG8,A.DG13,A.DG17 step#1 pm(>>,forward) area=13.50 rise=3.43 twist=26.8 strand#1 U DNA glyco-bond=-- sugar=-- nts=2 GG A.DG4,A.DG5 strand#2 U DNA glyco-bond=-- sugar=-- nts=2 GG A.DG7,A.DG8 strand#3 U DNA glyco-bond=-- sugar=-. nts=2 GG A.DG12,A.DG13 strand#4 U DNA glyco-bond=-- sugar=-- nts=2 GG A.DG16,A.DG17 loop#1 type=propeller strands=[#1,#2] nts=1 T A.DT6 loop#2 type=propeller strands=[#2,#3] nts=3 GTA A.DG9,A.DT10,A.DA11 loop#3 type=propeller strands=[#3,#4] nts=2 GT A.DG14,A.DT15 |
List of 1 non-stem G4-loop (including the two closing Gs)
1 type=lateral helix=#1 nts=19 GCTAGTCATTTTGACTAGG A.DG18,A.DC19,A.DT20,A.DA21,A.DG22,A.DT23,A.DC24,A.DA25,A.DT26,A.DT27,A.DT28,A.DT29,A.DG30,A.DA31,A.DC32,A.DT33,A.DA34,A.DG35,A.DG36