Summary information [schematics · tetrads · helices · stems · costacks · homepage]

PDB-id
6ac7
Class
DNA
Method
NMR
Summary
Structure of a (3+1) hybrid G-quadruplex in the parp1 promoter
Reference
Sengar, A., Vandana, J.J., Chambers, V.S., Di Antonio, M., Winnerdy, F.R., Balasubramanian, S., Phan, A.T.: (2019) "Structure of a (3+1) hybrid G-quadruplex in the PARP1 promoter." Nucleic Acids Res., 47, 1564-1572.
Abstract
Poly (ADP-ribose) polymerase 1 (PARP1) has emerged as an attractive target for cancer therapy due to its key role in DNA repair processes. Inhibition of PARP1 in BRCA-mutated cancers has been observed to be clinically beneficial. Recent genome-mapping experiments have identified a non-canonical G-quadruplex-forming sequence containing bulges within the PARP1 promoter. Structural features, like bulges, provide opportunities for selective chemical targeting of the non-canonical G-quadruplex structure within the PARP1 promoter, which could serve as an alternative therapeutic approach for the regulation of PARP1 expression. Here we report the G-quadruplex structure formed by a 23-nucleotide G-rich sequence in the PARP1 promoter. Our study revealed a three-layered intramolecular (3+1) hybrid G-quadruplex scaffold, in which three strands are oriented in one direction and the fourth in the opposite direction. This structure exhibits unique structural features such as an adenine bulge and a G·G·T base triple capping structure formed between the central edgewise loop, propeller loop and 5' flanking terminal. Given the highly important role of PARP1 in DNA repair and cancer intervention, this structure presents an attractive opportunity to explore the therapeutic potential of PARP1 inhibition via G-quadruplex DNA targeting.
G4 notes
3 G-tetrads, 1 G4 helix, 1 G4 stem · 3(-Lw-Ln-P), hybrid-2(3+1), UDUU

Base-block schematics in six views [summary · tetrads · helices · stems · costacks · homepage]

PyMOL session file PDB file View in 3Dmol.js

List of 3 G-tetrads [summary · schematics · helices · stems · costacks · homepage]

 1 glyco-bond=s-ss groove=wn-- planarity=0.137 type=planar nts=4 GGGG A.DG3,A.DG12,A.DG15,A.DG21
 2 glyco-bond=-s-- groove=wn-- planarity=0.149 type=planar nts=4 GGGG A.DG4,A.DG11,A.DG16,A.DG22
 3 glyco-bond=-s-- groove=wn-- planarity=0.093 type=planar nts=4 GGGG A.DG5,A.DG9,A.DG17,A.DG23

List of 1 G4-helix [summary · schematics · tetrads · stems · costacks · homepage]

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=s-ss groove=wn-- Major-->WC nts=4 GGGG A.DG3,A.DG12,A.DG15,A.DG21
 2  glyco-bond=-s-- groove=wn-- WC-->Major nts=4 GGGG A.DG4,A.DG11,A.DG16,A.DG22
 3  glyco-bond=-s-- groove=wn-- WC-->Major nts=4 GGGG A.DG5,A.DG9,A.DG17,A.DG23
  step#1  mm(<>,outward)  area=14.60 rise=3.99 twist=19.1
  step#2  pm(>>,forward)  area=11.12 rise=3.47 twist=33.6
  strand#1 DNA glyco-bond=s-- nts=3 GGG A.DG3,A.DG4,A.DG5
  strand#2 DNA glyco-bond=-ss nts=3 GGG A.DG12,A.DG11,A.DG9
  strand#3 DNA glyco-bond=s-- nts=3 GGG A.DG15,A.DG16,A.DG17
  strand#4 DNA glyco-bond=s-- nts=3 GGG A.DG21,A.DG22,A.DG23

Download PDB file
Interactive view in 3Dmol.js

2 stacking diagrams
 1  glyco-bond=s-ss groove=wn-- Major-->WC nts=4 GGGG A.DG3,A.DG12,A.DG15,A.DG21
2 glyco-bond=-s-- groove=wn-- WC-->Major nts=4 GGGG A.DG4,A.DG11,A.DG16,A.DG22
step#1 mm(<>,outward) area=14.60 rise=3.99 twist=19.1

Download PDB file
Interactive view in 3Dmol.js

 2  glyco-bond=-s-- groove=wn-- WC-->Major nts=4 GGGG A.DG4,A.DG11,A.DG16,A.DG22
3 glyco-bond=-s-- groove=wn-- WC-->Major nts=4 GGGG A.DG5,A.DG9,A.DG17,A.DG23
step#2 pm(>>,forward) area=11.12 rise=3.47 twist=33.6

Download PDB file
Interactive view in 3Dmol.js

List of 1 G4-stem [summary · schematics · tetrads · helices · costacks · homepage]

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-tetrad layers, 3 loops, INTRA-molecular, UDUU, anti-parallel, 3(-Lw-Ln-P), hybrid-2(3+1)

 1  glyco-bond=s-ss groove=wn-- Major-->WC nts=4 GGGG A.DG3,A.DG12,A.DG15,A.DG21
 2  glyco-bond=-s-- groove=wn-- WC-->Major nts=4 GGGG A.DG4,A.DG11,A.DG16,A.DG22
 3  glyco-bond=-s-- groove=wn-- WC-->Major nts=4 GGGG A.DG5,A.DG9,A.DG17,A.DG23
  step#1  mm(<>,outward)  area=14.60 rise=3.99 twist=19.1
  step#2  pm(>>,forward)  area=11.12 rise=3.47 twist=33.6
  strand#1  U DNA glyco-bond=s-- nts=3 GGG A.DG3,A.DG4,A.DG5
  strand#2* D DNA glyco-bond=-ss nts=3 GGG A.DG12,A.DG11,A.DG9 bulged-nts=1 A A.DA10
  strand#3  U DNA glyco-bond=s-- nts=3 GGG A.DG15,A.DG16,A.DG17
  strand#4  U DNA glyco-bond=s-- nts=3 GGG A.DG21,A.DG22,A.DG23
  loop#1 type=lateral   strands=[#1,#2] nts=3 TCC A.DT6,A.DC7,A.DC8
  loop#2 type=lateral   strands=[#2,#3] nts=2 CG A.DC13,A.DG14
  loop#3 type=propeller strands=[#3,#4] nts=3 CTT A.DC18,A.DT19,A.DT20

Download PDB file
Interactive view in 3Dmol.js

List of 0 G4 coaxial stacks [summary · schematics · tetrads · helices · stems · homepage]

List of 0 non-stem G4-loops (including the two closing Gs)