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

PDB-id
6ia4
Class
DNA
Method
NMR
Summary
Human telomeric G-quadruplex with 8-oxo-g substitution in the outer 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.
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 oxo G'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 nonsubstituted 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(-P-Lw-Ln), hybrid-1(3+1), UUDU

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=ss-s groove=-wn- planarity=0.238 type=other  nts=4 GGGg A.DG3,A.DG9,A.DG17,A.8OG21
 2 glyco-bond=--s- groove=-wn- planarity=0.179 type=other  nts=4 GGGG A.DG4,A.DG10,A.DG16,A.DG22
 3 glyco-bond=--s- groove=-wn- planarity=0.476 type=bowl   nts=4 GGGG A.DG5,A.DG11,A.DG15,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=ss-s groove=-wn- Major-->WC nts=4 GGGg A.DG3,A.DG9,A.DG17,A.8OG21
 2  glyco-bond=--s- groove=-wn- WC-->Major nts=4 GGGG A.DG4,A.DG10,A.DG16,A.DG22
 3  glyco-bond=--s- groove=-wn- WC-->Major nts=4 GGGG A.DG5,A.DG11,A.DG15,A.DG23
  step#1  mm(<>,outward)  area=20.34 rise=3.48 twist=15.3
  step#2  pm(>>,forward)  area=11.06 rise=3.61 twist=23.7
  strand#1 DNA glyco-bond=s-- nts=3 GGG A.DG3,A.DG4,A.DG5
  strand#2 DNA glyco-bond=s-- nts=3 GGG A.DG9,A.DG10,A.DG11
  strand#3 DNA glyco-bond=-ss nts=3 GGG A.DG17,A.DG16,A.DG15
  strand#4 DNA glyco-bond=s-- nts=3 gGG A.8OG21,A.DG22,A.DG23

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2 stacking diagrams
 1  glyco-bond=ss-s groove=-wn- Major-->WC nts=4 GGGg A.DG3,A.DG9,A.DG17,A.8OG21
2 glyco-bond=--s- groove=-wn- WC-->Major nts=4 GGGG A.DG4,A.DG10,A.DG16,A.DG22
step#1 mm(<>,outward) area=20.34 rise=3.48 twist=15.3

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 2  glyco-bond=--s- groove=-wn- WC-->Major nts=4 GGGG A.DG4,A.DG10,A.DG16,A.DG22
3 glyco-bond=--s- groove=-wn- WC-->Major nts=4 GGGG A.DG5,A.DG11,A.DG15,A.DG23
step#2 pm(>>,forward) area=11.06 rise=3.61 twist=23.7

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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, UUDU, anti-parallel, 3(-P-Lw-Ln), hybrid-1(3+1)

 1  glyco-bond=ss-s groove=-wn- Major-->WC nts=4 GGGg A.DG3,A.DG9,A.DG17,A.8OG21
 2  glyco-bond=--s- groove=-wn- WC-->Major nts=4 GGGG A.DG4,A.DG10,A.DG16,A.DG22
 3  glyco-bond=--s- groove=-wn- WC-->Major nts=4 GGGG A.DG5,A.DG11,A.DG15,A.DG23
  step#1  mm(<>,outward)  area=20.34 rise=3.48 twist=15.3
  step#2  pm(>>,forward)  area=11.06 rise=3.61 twist=23.7
  strand#1  U DNA glyco-bond=s-- nts=3 GGG A.DG3,A.DG4,A.DG5
  strand#2  U DNA glyco-bond=s-- nts=3 GGG A.DG9,A.DG10,A.DG11
  strand#3  D DNA glyco-bond=-ss nts=3 GGG A.DG17,A.DG16,A.DG15
  strand#4  U DNA glyco-bond=s-- nts=3 gGG A.8OG21,A.DG22,A.DG23
  loop#1 type=propeller 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=lateral   strands=[#3,#4] nts=3 TTA A.DT18,A.DT19,A.DA20

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

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