Summary information

PDB id
8abd
Class
DNA
Method
NMR
Summary
Solution structure of phen-dc3 intercalating into a quadruplex-duplex hybrid
Reference
Vianney YM, Weisz K (2022): "High-affinity binding at quadruplex-duplex junctions: rather the rule than the exception." Nucleic Acids Res., 50, 11948-11964. doi: 10.1093/nar/gkac1088.
Abstract
Quadruplex-duplex (Q-D) junctions constitute unique structural motifs in genomic sequences. Through comprehensive calorimetric as well as high-resolution NMR structural studies, Q-D junctions with a hairpin-type snapback loop coaxially stacked onto an outer G-tetrad were identified to be most effective binding sites for various polycyclic quadruplex ligands. The Q-D interface is readily recognized by intercalation of the ligand aromatic core structure between G-tetrad and the neighboring base pair. Based on the thermodynamic and structural data, guidelines for the design of ligands with enhanced selectivity towards a Q-D interface emerge. Whereas intercalation at Q-D junctions mostly outcompete stacking at the quadruplex free outer tetrad or intercalation between duplex base pairs to varying degrees, ligand side chains considerably contribute to the selectivity for a Q-D target over other binding sites. In contrast to common perceptions, an appended side chain that additionally interacts within the duplex minor groove may confer only poor selectivity. Rather, the Q-D selectivity is suggested to benefit from an extension of the side chain towards the exposed part of the G-tetrad at the junction. The presented results will support the design of selective high-affinity binding ligands for targeting Q-D interfaces in medicinal but also technological applications.
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=0.257 type=other  nts=4 GGGG A.DG4,A.DG7,A.DG12,A.DG16
 2 glyco-bond=---- sugar=---- groove=---- planarity=0.144 type=planar nts=4 GGGG A.DG5,A.DG8,A.DG13,A.DG17
 3 glyco-bond=---s sugar=---- groove=--wn planarity=0.185 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=13.12 rise=3.44 twist=27.6
  step#2  pm(>>,forward)  area=14.44 rise=3.41 twist=25.6
  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=13.12 rise=3.44 twist=27.6

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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=14.44 rise=3.41 twist=25.6

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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=13.12 rise=3.44 twist=27.6
  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