Summary information

PDB id
6ia0
Class
DNA
Method
NMR
Summary
Human telomeric g-quadruplex with 8-oxo-g substitution in the central g-quartet
Reference
Bielskute S, Plavec J, Podbevsek P (2019): "Impact of Oxidative Lesions on the Human Telomeric G-Quadruplex." J. Am. Chem. Soc., 141, 2594-2603. doi: 10.1021/jacs.8b12748.
Abstract
Telomere attrition is closely associated with cell aging and exposure to reactive oxygen species (ROS). While oxidation products of nucleotides have been studied extensively in the past the underlying secondary/tertiary structural changes in DNA remain poorly understood. In this work we systematically probed guanine positions in the human telomeric oligonucleotide sequence (hTel) by substitutions with the major product of ROS - 8-oxo-7,8-dihydroguanine (oxoG) - and evaluated the G-quadruplex forming ability of such oligonucleotides. Due to reduced hydrogen bonding capability caused by oxoG a loss of G-quadruplex structure was observed for most oligonucleotides containing oxidative lesions. However, some positions in the hTel sequence were found to tolerate substitutions with oxoG. Due to oxoG's preference for the syn conformation, distinct responses were observed when replacing guanines with different glycosidic conformations. Accommodation of oxoG at sites originally in syn or anti in non-substituted hTel G-quadruplex requires a minor structural rearrangement or a major conformational shift, respectively. The system responds by retaining or switching to a fold where oxoG is in syn conformation. Most importantly, these G-quadruplex structures are still stable at physiological temperatures and should be considered detrimental in higher-order telomere structures.
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

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List of 3 G-tetrads

 1 glyco-bond=-s-- sugar=---- groove=wn-- planarity=0.437 type=other  nts=4 GGGG A.DG3,A.DG11,A.DG15,A.DG21
 2 glyco-bond=-s-- sugar=---- groove=wn-- planarity=0.263 type=saddle nts=4 GgGG A.DG4,A.8OG10,A.DG16,A.DG22
 3 glyco-bond=-s-- sugar=---- groove=wn-- planarity=0.233 type=other  nts=4 GGGG A.DG5,A.DG9,A.DG17,A.DG23

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=-s-- sugar=---- groove=wn-- WC-->Major nts=4 GGGG A.DG3,A.DG11,A.DG15,A.DG21
 2  glyco-bond=-s-- sugar=---- groove=wn-- WC-->Major nts=4 GgGG A.DG4,A.8OG10,A.DG16,A.DG22
 3  glyco-bond=-s-- sugar=---- groove=wn-- WC-->Major nts=4 GGGG A.DG5,A.DG9,A.DG17,A.DG23
  step#1  pm(>>,forward)  area=22.82 rise=3.43 twist=18.4
  step#2  pm(>>,forward)  area=12.17 rise=3.27 twist=27.4
  strand#1 DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG3,A.DG4,A.DG5
  strand#2 DNA glyco-bond=sss sugar=--- nts=3 GgG A.DG11,A.8OG10,A.DG9
  strand#3 DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG15,A.DG16,A.DG17
  strand#4 DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG21,A.DG22,A.DG23

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2 stacking diagrams
 1  glyco-bond=-s-- sugar=---- groove=wn-- WC-->Major nts=4 GGGG A.DG3,A.DG11,A.DG15,A.DG21
2 glyco-bond=-s-- sugar=---- groove=wn-- WC-->Major nts=4 GgGG A.DG4,A.8OG10,A.DG16,A.DG22
step#1 pm(>>,forward) area=22.82 rise=3.43 twist=18.4

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 2  glyco-bond=-s-- sugar=---- groove=wn-- WC-->Major nts=4 GgGG A.DG4,A.8OG10,A.DG16,A.DG22
3 glyco-bond=-s-- sugar=---- groove=wn-- WC-->Major nts=4 GGGG A.DG5,A.DG9,A.DG17,A.DG23
step#2 pm(>>,forward) area=12.17 rise=3.27 twist=27.4

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

 1  glyco-bond=-s-- sugar=---- groove=wn-- WC-->Major nts=4 GGGG A.DG3,A.DG11,A.DG15,A.DG21
 2  glyco-bond=-s-- sugar=---- groove=wn-- WC-->Major nts=4 GgGG A.DG4,A.8OG10,A.DG16,A.DG22
 3  glyco-bond=-s-- sugar=---- groove=wn-- WC-->Major nts=4 GGGG A.DG5,A.DG9,A.DG17,A.DG23
  step#1  pm(>>,forward)  area=22.82 rise=3.43 twist=18.4
  step#2  pm(>>,forward)  area=12.17 rise=3.27 twist=27.4
  strand#1  U DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG3,A.DG4,A.DG5
  strand#2  D DNA glyco-bond=sss sugar=--- nts=3 GgG A.DG11,A.8OG10,A.DG9
  strand#3  U DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG15,A.DG16,A.DG17
  strand#4  U DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG21,A.DG22,A.DG23
  loop#1 type=lateral   strands=[#1,#2] nts=3 TTA A.DT6,A.DT7,A.DA8
  loop#2 type=lateral   strands=[#2,#3] nts=3 TTA A.DT12,A.DT13,A.DA14
  loop#3 type=propeller strands=[#3,#4] nts=3 TTA A.DT18,A.DT19,A.DA20

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