Summary information

PDB id
8abn
Class
DNA
Method
NMR
Summary
Solution structure of a phenyl-indoloquinoline 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
2 G-tetrads, 1 G4 helix, 1 G4 stem, 2(+Ln+Lw+Ln), chair(2+2), UDUD

Base-block schematics in six views

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List of 2 G-tetrads

 1 glyco-bond=s-s- sugar=---- groove=wnwn planarity=0.353 type=saddle nts=4 GGGG A.DG1,A.DG27,A.DG22,A.DG6
 2 glyco-bond=-s-s sugar=---- groove=wnwn planarity=0.407 type=bowl   nts=4 GGGG A.DG2,A.DG26,A.DG23,A.DG5

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, 2 G-tetrad layers, INTRA-molecular, with 1 stem

 1  glyco-bond=s-s- sugar=---- groove=wnwn Major-->WC nts=4 GGGG A.DG1,A.DG27,A.DG22,A.DG6
 2  glyco-bond=-s-s sugar=---- groove=wnwn WC-->Major nts=4 GGGG A.DG2,A.DG26,A.DG23,A.DG5
  step#1  mm(<>,outward)  area=18.73 rise=3.49 twist=14.6
  strand#1 DNA glyco-bond=s- sugar=-- nts=2 GG A.DG1,A.DG2
  strand#2 DNA glyco-bond=-s sugar=-- nts=2 GG A.DG27,A.DG26
  strand#3 DNA glyco-bond=s- sugar=-- nts=2 GG A.DG22,A.DG23
  strand#4 DNA glyco-bond=-s sugar=-- nts=2 GG A.DG6,A.DG5

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1 stacking diagram 
 1  glyco-bond=s-s- sugar=---- groove=wnwn Major-->WC nts=4 GGGG A.DG1,A.DG27,A.DG22,A.DG6
 2  glyco-bond=-s-s sugar=---- groove=wnwn WC-->Major nts=4 GGGG A.DG2,A.DG26,A.DG23,A.DG5
  step#1  mm(<>,outward)  area=18.73 rise=3.49 twist=14.6

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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, UDUD, anti-parallel, 2(+Ln+Lw+Ln), chair(2+2)

 1  glyco-bond=s-s- sugar=---- groove=wnwn Major-->WC nts=4 GGGG A.DG1,A.DG27,A.DG22,A.DG6
 2  glyco-bond=-s-s sugar=---- groove=wnwn WC-->Major nts=4 GGGG A.DG2,A.DG26,A.DG23,A.DG5
  step#1  mm(<>,outward)  area=18.73 rise=3.49 twist=14.6
  strand#1  U DNA glyco-bond=s- sugar=-- nts=2 GG A.DG1,A.DG2
  strand#2  D DNA glyco-bond=-s sugar=-- nts=2 GG A.DG27,A.DG26
  strand#3  U DNA glyco-bond=s- sugar=-- nts=2 GG A.DG22,A.DG23
  strand#4  D DNA glyco-bond=-s sugar=-- nts=2 GG A.DG6,A.DG5
  loop#1 type=lateral   strands=[#1,#4] nts=2 TT A.DT3,A.DT4
  loop#2 type=lateral   strands=[#4,#3] nts=15 CGCGAAGCATTCGCG A.DC7,A.DG8,A.DC9,A.DG10,A.DA11,A.DA12,A.DG13,A.DC14,A.DA15,A.DT16,A.DT17,A.DC18,A.DG19,A.DC20,A.DG21
  loop#3 type=lateral   strands=[#3,#2] nts=2 TT A.DT24,A.DT25

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