Summary information

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 (2021): "Indoloquinoline Ligands Favor Intercalation at Quadruplex-Duplex Interfaces." Chemistry, 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 7 M -1 and large exothermicities Δ H ° of -14 kcal/mol in a 120 mM K + 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 N 5-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, 2(-P-P-P), parallel(4+0), UUUU

Base-block schematics in six views

PyMOL session file PDB file View in 3Dmol.js

List of 3 G-tetrads

 1 glyco-bond=---- sugar=---- groove=---- planarity=0.347 type=other  nts=4 GGGG A.DG4,A.DG7,A.DG12,A.DG16
 2 glyco-bond=---- sugar=--.- groove=---- planarity=0.349 type=saddle nts=4 GGGG A.DG5,A.DG8,A.DG13,A.DG17
 3 glyco-bond=---s sugar=---- groove=--wn planarity=0.281 type=other  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-tetrad layers, INTRA-molecular, with 1 stem

 1  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG4,A.DG7,A.DG12,A.DG16
 2  glyco-bond=---- sugar=--.- groove=---- WC-->Major nts=4 GGGG A.DG5,A.DG8,A.DG13,A.DG17
 3  glyco-bond=s--- sugar=---- groove=n--w WC-->Major 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

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2 stacking diagrams
 1  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG4,A.DG7,A.DG12,A.DG16
2 glyco-bond=---- sugar=--.- groove=---- WC-->Major nts=4 GGGG A.DG5,A.DG8,A.DG13,A.DG17
step#1 pm(>>,forward) area=13.50 rise=3.43 twist=26.8

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 2  glyco-bond=---- sugar=--.- groove=---- WC-->Major nts=4 GGGG A.DG5,A.DG8,A.DG13,A.DG17
3 glyco-bond=s--- sugar=---- groove=n--w WC-->Major nts=4 GGGG A.DG36,A.DG9,A.DG14,A.DG18
step#2 pm(>>,forward) area=11.20 rise=3.47 twist=29.9

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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, 2 G-tetrad layers, 3 loops, INTRA-molecular, UUUU, parallel, 2(-P-P-P), parallel(4+0)

 1  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG4,A.DG7,A.DG12,A.DG16
 2  glyco-bond=---- sugar=--.- groove=---- WC-->Major 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

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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