Summary information and primary citation

PDB-id
2mwz
Class
DNA
Method
NMR
Summary
Xanthine and 8-oxoguanine in g-quadruplexes: formation of a g g x o tetrad
Reference
Cheong VV, Heddi B, Lech CJ, Phan AT (2015): "Xanthine and 8-oxoguanine in G-quadruplexes: formation of a GGXO tetrad." Nucleic Acids Res., 43, 10506-10514. doi: 10.1093/nar/gkv826.
Abstract
G-quadruplexes are four-stranded structures built from stacked G-tetrads (G·G·G·G), which are planar cyclical assemblies of four guanine bases interacting through Hoogsteen hydrogen bonds. A G-quadruplex containing a single guanine analog substitution, such as 8-oxoguanine (O) or xanthine (X), would suffer from a loss of a Hoogsteen hydrogen bond within a G-tetrad and/or potential steric hindrance. We show that a proper arrangement of O and X bases can reestablish the hydrogen-bond pattern within a G·G·X·O tetrad. Rational incorporation of G·G·X·O tetrads in a (3+1) G-quadruplex demonstrated a similar folding topology and thermal stability to that of the unmodified G-quadruplex. pH titration conducted on X·O-modified G-quadruplexes indicated a protonation-deprotonation equilibrium of X with a pKa ∼6.7. The solution structure of a G-quadruplex containing a G·G·X·O tetrad was determined, displaying the same folding topology in both the protonated and deprotonated states. A G-quadruplex containing a deprotonated X·O pair was shown to exhibit a more electronegative groove compared to that of the unmodified one. These differences are likely to manifest in the electronic properties of G-quadruplexes and may have important implications for drug targeting and DNA-protein interactions.
G4 notes
3 G-tetrads, 1 G4 helix, 1 G4 stem, UUDU, hybrid1, 3+1, 3(-P-Lw-Ln)

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List of 3 G-tetrads

 1 glyco-bond=ss-s sugar=---- groove=-wn- planarity=0.196 type=other  O- nts=4 GggG A.DG3,A.8OG9,A.3ZO17,A.DG21
 2 glyco-bond=--s- sugar=--.- groove=-wn- planarity=0.195 type=other  O+ nts=4 GGGG A.DG4,A.DG10,A.DG16,A.DG22
 3 glyco-bond=--s- sugar=---. groove=-wn- planarity=0.389 type=bowl   O+ nts=4 GGGG A.DG5,A.DG11,A.DG15,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-tetrads, INTRA-molecular, with 1 stem
 1  glyco-bond=ss-s sugar=---- groove=-wn- Major-->WC O- nts=4 GggG A.DG3,A.8OG9,A.3ZO17,A.DG21
 2  glyco-bond=--s- sugar=--.- groove=-wn- WC-->Major O+ nts=4 GGGG A.DG4,A.DG10,A.DG16,A.DG22
 3  glyco-bond=--s- sugar=---. groove=-wn- WC-->Major O+ nts=4 GGGG A.DG5,A.DG11,A.DG15,A.DG23
  step#1  mm(<>,outward)  area=19.47 rise=3.63 twist=12.9
  step#2  pm(>>,forward)  area=11.53 rise=3.45 twist=25.1
  strand#1 DNA glyco-bond=s-- sugar=--- nts=3 GGG A.DG3,A.DG4,A.DG5
  strand#2 DNA glyco-bond=s-- sugar=--- nts=3 gGG A.8OG9,A.DG10,A.DG11
  strand#3 DNA glyco-bond=-ss sugar=-.- nts=3 gGG A.3ZO17,A.DG16,A.DG15
  strand#4 DNA glyco-bond=s-- sugar=--. nts=3 GGG A.DG21,A.DG22,A.DG23

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2 stacking diagrams 
 1  glyco-bond=ss-s sugar=---- groove=-wn- Major-->WC O- nts=4 GggG A.DG3,A.8OG9,A.3ZO17,A.DG21
 2  glyco-bond=--s- sugar=--.- groove=-wn- WC-->Major O+ nts=4 GGGG A.DG4,A.DG10,A.DG16,A.DG22
  step#1  mm(<>,outward)  area=19.47 rise=3.63 twist=12.9

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 2  glyco-bond=--s- sugar=--.- groove=-wn- WC-->Major O+ nts=4 GGGG A.DG4,A.DG10,A.DG16,A.DG22
 3  glyco-bond=--s- sugar=---. groove=-wn- WC-->Major O+ nts=4 GGGG A.DG5,A.DG11,A.DG15,A.DG23
  step#2  pm(>>,forward)  area=11.53 rise=3.45 twist=25.1

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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-tetrads, 3 loops, INTRA-molecular, UUDU, hybrid1, 3+1, 3(-P-Lw-Ln)
 1  glyco-bond=ss-s sugar=---- groove=-wn- Major-->WC O- nts=4 GggG A.DG3,A.8OG9,A.3ZO17,A.DG21
 2  glyco-bond=--s- sugar=--.- groove=-wn- WC-->Major O+ nts=4 GGGG A.DG4,A.DG10,A.DG16,A.DG22
 3  glyco-bond=--s- sugar=---. groove=-wn- WC-->Major O+ nts=4 GGGG A.DG5,A.DG11,A.DG15,A.DG23
  step#1  mm(<>,outward)  area=19.47 rise=3.63 twist=12.9
  step#2  pm(>>,forward)  area=11.53 rise=3.45 twist=25.1
  strand#1  U DNA glyco-bond=s-- sugar=--- nts=3 GGG A.DG3,A.DG4,A.DG5
  strand#2  U DNA glyco-bond=s-- sugar=--- nts=3 gGG A.8OG9,A.DG10,A.DG11
  strand#3  D DNA glyco-bond=-ss sugar=-.- nts=3 gGG A.3ZO17,A.DG16,A.DG15
  strand#4  U DNA glyco-bond=s-- sugar=--. nts=3 GGG A.DG21,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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