Summary information

PDB id
6zx6
Class
DNA
Method
NMR
Summary
Antiparallel basket-type g-quadruplex DNA structure formed in human bcl-2 promoter containing 8-oxog
Reference
Bielskute S, Plavec J, Podbevsek P (2021): "Oxidative lesions modulate G-quadruplex stability and structure in the human BCL2 promoter." Nucleic Acids Res., 49, 2346-2356. doi: 10.1093/nar/gkab057.
Abstract
Misregulation of BCL2 expression has been observed with many diseases and is associated with cellular exposure to reactive oxygen species. A region upstream of the P1 promoter in the human BCL2 gene plays a major role in regulating transcription. This G/C-rich region is highly polymorphic and capable of forming G-quadruplex structures. Herein we report that an oxidative event simulated with an 8-oxo-7,8-dihydroguanine (oxoG) substitution within a long G-tract results in a reduction of structural polymorphism. Surprisingly, oxoG within a 25-nt construct boosts thermal stability of the resulting G-quadruplex. This is achieved by distinct hydrogen bonding properties of oxoG, which facilitate formation of an antiparallel basket-type G-quadruplex with a three G-quartet core and a G·oxoG·C base triad. While oxoG has previously been considered detrimental for G-quadruplex formation, its stabilizing effect within a promoter described in this study suggests a potential novel regulatory role of oxidative stress in general and specifically in BCL2 gene transcription.
G4 notes
3 G-tetrads, 1 G4 helix, 1 G4 stem, 3(-LwD+Ln), basket(2+2), UDDU

Base-block schematics in six views

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List of 3 G-tetrads

 1 glyco-bond=s--s sugar=---- groove=w-n- planarity=0.394 type=other  nts=4 GGGG A.DG2,A.DG10,A.DG24,A.DG16
 2 glyco-bond=-ss- sugar=---- groove=w-n- planarity=0.423 type=other  nts=4 GGGG A.DG3,A.DG9,A.DG23,A.DG17
 3 glyco-bond=s--s sugar=-.-- groove=w-n- planarity=0.517 type=other  nts=4 GGGG A.DG4,A.DG8,A.DG22,A.DG18

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--s sugar=---- groove=w-n- Major-->WC nts=4 GGGG A.DG2,A.DG10,A.DG24,A.DG16
 2  glyco-bond=-ss- sugar=---- groove=w-n- WC-->Major nts=4 GGGG A.DG3,A.DG9,A.DG23,A.DG17
 3  glyco-bond=s--s sugar=-.-- groove=w-n- Major-->WC nts=4 GGGG A.DG4,A.DG8,A.DG22,A.DG18
  step#1  mm(<>,outward)  area=14.17 rise=3.45 twist=19.4
  step#2  pp(><,inward)   area=13.71 rise=3.44 twist=32.1
  strand#1 DNA glyco-bond=s-s sugar=--- nts=3 GGG A.DG2,A.DG3,A.DG4
  strand#2 DNA glyco-bond=-s- sugar=--. nts=3 GGG A.DG10,A.DG9,A.DG8
  strand#3 DNA glyco-bond=-s- sugar=--- nts=3 GGG A.DG24,A.DG23,A.DG22
  strand#4 DNA glyco-bond=s-s sugar=--- nts=3 GGG A.DG16,A.DG17,A.DG18

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2 stacking diagrams 
 1  glyco-bond=s--s sugar=---- groove=w-n- Major-->WC nts=4 GGGG A.DG2,A.DG10,A.DG24,A.DG16
 2  glyco-bond=-ss- sugar=---- groove=w-n- WC-->Major nts=4 GGGG A.DG3,A.DG9,A.DG23,A.DG17
  step#1  mm(<>,outward)  area=14.17 rise=3.45 twist=19.4

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 2  glyco-bond=-ss- sugar=---- groove=w-n- WC-->Major nts=4 GGGG A.DG3,A.DG9,A.DG23,A.DG17
 3  glyco-bond=s--s sugar=-.-- groove=w-n- Major-->WC nts=4 GGGG A.DG4,A.DG8,A.DG22,A.DG18
  step#2  pp(><,inward)   area=13.71 rise=3.44 twist=32.1

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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, UDDU, anti-parallel, 3(-LwD+Ln), basket(2+2)

 1  glyco-bond=s--s sugar=---- groove=w-n- Major-->WC nts=4 GGGG A.DG2,A.DG10,A.DG24,A.DG16
 2  glyco-bond=-ss- sugar=---- groove=w-n- WC-->Major nts=4 GGGG A.DG3,A.DG9,A.DG23,A.DG17
 3  glyco-bond=s--s sugar=-.-- groove=w-n- Major-->WC nts=4 GGGG A.DG4,A.DG8,A.DG22,A.DG18
  step#1  mm(<>,outward)  area=14.17 rise=3.45 twist=19.4
  step#2  pp(><,inward)   area=13.71 rise=3.44 twist=32.1
  strand#1  U DNA glyco-bond=s-s sugar=--- nts=3 GGG A.DG2,A.DG3,A.DG4
  strand#2  D DNA glyco-bond=-s- sugar=--. nts=3 GGG A.DG10,A.DG9,A.DG8
  strand#3  D DNA glyco-bond=-s- sugar=--- nts=3 GGG A.DG24,A.DG23,A.DG22
  strand#4  U DNA glyco-bond=s-s sugar=--- nts=3 GGG A.DG16,A.DG17,A.DG18
  loop#1 type=lateral   strands=[#1,#2] nts=3 CGC A.DC5,A.DG6,A.DC7
  loop#2 type=diagonal  strands=[#2,#4] nts=5 AGGAA A.DA11,A.DG12,A.DG13,A.DA14,A.DA15
  loop#3 type=lateral   strands=[#4,#3] nts=3 gGC A.8OG19,A.DG20,A.DC21

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