DSSR-enabled G4 identification/annotation

Summary information and primary citation

PDB-id: 5ua3
Class: DNA
Method: X-ray (1.88 Å)
Summary: Crystal structure of a DNA g-quadruplex with a cytosine bulge
Reference: Meier M, Moya-Torres A, Krahn NJ, McDougall MD, Orriss GL, McRae EKS, Booy EP, McEleney K, Patel TR, McKenna SA, Stetefeld J (2018): "Structure and hydrodynamics of a DNA G-quadruplex with a cytosine bulge." Nucleic Acids Res., 46, 5319-5331. doi: 10.1093/nar/gky307.
Abstract: The identification of four-stranded G-quadruplexes (G4s) has highlighted the fact that DNA has additional spatial organisations at its disposal other than double-stranded helices. Recently, it became clear that the formation of G4s is not limited to the traditional G3+NL1G3+NL2G3+NL3G3+ sequence motif. Instead, the G3 triplets can be interrupted by deoxythymidylate (DNA) or uridylate (RNA) where the base forms a bulge that loops out from the G-quadruplex core. Here, we report the first high-resolution X-ray structure of a unique unimolecular DNA G4 with a cytosine bulge. The G4 forms a dimer that is stacked via its 5'-tetrads. Analytical ultracentrifugation, static light scattering and small angle X-ray scattering confirmed that the G4 adapts a predominantly dimeric structure in solution. We provide a comprehensive comparison of previously published G4 structures containing bulges and report a special γ torsion angle range preferentially populated by the G4 core guanylates adjacent to bulges. Since the penalty for introducing bulges appears to be negligible, it should be possible to functionalize G4s by introducing artificial or modified nucleotides at such positions. The presence of the bulge alters the surface of the DNA, providing an opportunity to develop drugs that can specifically target individual G4s.
G4 notes: 6 G-tetrads, 1 G4 helix, 2 G4 stems, 1 G4 coaxial stack, 3(-P-P-P), parallel(4+0), UUUU, coaxial interfaces: 5'/5'

Cartoon-block schematics in six views (download the tarball)

List of 6 G-tetrads

 1 glyco-bond=---- sugar=---- groove=---- planarity=0.097 type=planar O+ nts=4 GGGG A.DG1,A.DG6,A.DG11,A.DG15
 2 glyco-bond=---- sugar=-3-- groove=---- planarity=0.195 type=bowl-2 O+ nts=4 GGGG A.DG2,A.DG8,A.DG12,A.DG16
 3 glyco-bond=---- sugar=---- groove=---- planarity=0.229 type=bowl   O+ nts=4 GGGG A.DG3,A.DG9,A.DG13,A.DG17
 4 glyco-bond=---- sugar=---- groove=---- planarity=0.088 type=planar O+ nts=4 GGGG B.DG1,B.DG6,B.DG11,B.DG15
 5 glyco-bond=---- sugar=-3-- groove=---- planarity=0.171 type=bowl-2 O+ nts=4 GGGG B.DG2,B.DG8,B.DG12,B.DG16
 6 glyco-bond=---- sugar=---- groove=---- planarity=0.275 type=bowl   O+ nts=4 GGGG B.DG3,B.DG9,B.DG13,B.DG17

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, 6 G-tetrads, inter-molecular, with 2 stems

	1 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG3,A.DG9,A.DG13,A.DG17 2 glyco-bond=---- sugar=-3-- groove=---- WC-->Major O+ nts=4 GGGG A.DG2,A.DG8,A.DG12,A.DG16 3* glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG1,A.DG6,A.DG11,A.DG15 4 glyco-bond=---- sugar=---- groove=---- Major-->WC O+ nts=4 GGGG B.DG6,B.DG1,B.DG15,B.DG11 5 glyco-bond=---- sugar=3--- groove=---- Major-->WC O+ nts=4 GGGG B.DG8,B.DG2,B.DG16,B.DG12 6 glyco-bond=---- sugar=---- groove=---- Major-->WC O+ nts=4 GGGG B.DG9,B.DG3,B.DG17,B.DG13 step#1 mp(<<,backward) area=9.89 rise=3.42 twist=30.1 step#2 mp(<<,backward) area=10.82 rise=3.35 twist=30.1 step#3 mm(<>,outward) area=28.50 rise=3.32 twist=-9.1 step#4 pm(>>,forward) area=10.39 rise=3.31 twist=31.0 step#5 pm(>>,forward) area=9.91 rise=3.41 twist=29.4 strand#1 DNA glyco-bond=------ sugar=----3- nts=6 GGGGGG A.DG3,A.DG2,A.DG1,B.DG6,B.DG8,B.DG9 strand#2 DNA glyco-bond=------ sugar=-3---- nts=6 GGGGGG A.DG9,A.DG8,A.DG6,B.DG1,B.DG2,B.DG3 strand#3 DNA glyco-bond=------ sugar=------ nts=6 GGGGGG A.DG13,A.DG12,A.DG11,B.DG15,B.DG16,B.DG17 strand#4 DNA glyco-bond=------ sugar=------ nts=6 GGGGGG A.DG17,A.DG16,A.DG15,B.DG11,B.DG12,B.DG13 Download PDB file Interactive view in 3Dmol.js
5 stacking diagrams
	1 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG3,A.DG9,A.DG13,A.DG17 2 glyco-bond=---- sugar=-3-- groove=---- WC-->Major O+ nts=4 GGGG A.DG2,A.DG8,A.DG12,A.DG16 step#1 mp(<<,backward) area=9.89 rise=3.42 twist=30.1 Download PDB file Interactive view in 3Dmol.js
	2 glyco-bond=---- sugar=-3-- groove=---- WC-->Major O+ nts=4 GGGG A.DG2,A.DG8,A.DG12,A.DG16 3* glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG1,A.DG6,A.DG11,A.DG15 step#2 mp(<<,backward) area=10.82 rise=3.35 twist=30.1 Download PDB file Interactive view in 3Dmol.js
	3* glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG1,A.DG6,A.DG11,A.DG15 4 glyco-bond=---- sugar=---- groove=---- Major-->WC O+ nts=4 GGGG B.DG6,B.DG1,B.DG15,B.DG11 step#3 mm(<>,outward) area=28.50 rise=3.32 twist=-9.1 Download PDB file Interactive view in 3Dmol.js
	4 glyco-bond=---- sugar=---- groove=---- Major-->WC O+ nts=4 GGGG B.DG6,B.DG1,B.DG15,B.DG11 5 glyco-bond=---- sugar=3--- groove=---- Major-->WC O+ nts=4 GGGG B.DG8,B.DG2,B.DG16,B.DG12 step#4 pm(>>,forward) area=10.39 rise=3.31 twist=31.0 Download PDB file Interactive view in 3Dmol.js
	5 glyco-bond=---- sugar=3--- groove=---- Major-->WC O+ nts=4 GGGG B.DG8,B.DG2,B.DG16,B.DG12 6 glyco-bond=---- sugar=---- groove=---- Major-->WC O+ nts=4 GGGG B.DG9,B.DG3,B.DG17,B.DG13 step#5 pm(>>,forward) area=9.91 rise=3.41 twist=29.4 Download PDB file Interactive view in 3Dmol.js

List of 2 G4-stems

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, UUUU, parallel, 3(-P-P-P), parallel(4+0)

 1  glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG1,A.DG6,A.DG11,A.DG15
 2  glyco-bond=---- sugar=-3-- groove=---- WC-->Major O+ nts=4 GGGG A.DG2,A.DG8,A.DG12,A.DG16
 3  glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG3,A.DG9,A.DG13,A.DG17
  step#1  pm(>>,forward)  area=10.82 rise=3.35 twist=30.1
  step#2  pm(>>,forward)  area=9.89  rise=3.42 twist=30.1
  strand#1  U DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG1,A.DG2,A.DG3
  strand#2* U DNA glyco-bond=--- sugar=-3- nts=3 GGG A.DG6,A.DG8,A.DG9 bulged-nts=1 C A.DC7
  strand#3  U DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG11,A.DG12,A.DG13
  strand#4  U DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG15,A.DG16,A.DG17
  loop#1 type=propeller strands=[#1,#2] nts=2 TT A.DT4,A.DT5
  loop#2 type=propeller strands=[#2,#3] nts=1 A A.DA10
  loop#3 type=propeller strands=[#3,#4] nts=1 T A.DT14

Download PDB file
Interactive view in 3Dmol.js

Stem#2, 3 G-tetrads, 3 loops, INTRA-molecular, UUUU, parallel, 3(-P-P-P), parallel(4+0)

 1  glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG B.DG1,B.DG6,B.DG11,B.DG15
 2  glyco-bond=---- sugar=-3-- groove=---- WC-->Major O+ nts=4 GGGG B.DG2,B.DG8,B.DG12,B.DG16
 3  glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG B.DG3,B.DG9,B.DG13,B.DG17
  step#1  pm(>>,forward)  area=10.39 rise=3.31 twist=31.0
  step#2  pm(>>,forward)  area=9.91  rise=3.41 twist=29.4
  strand#1  U DNA glyco-bond=--- sugar=--- nts=3 GGG B.DG1,B.DG2,B.DG3
  strand#2* U DNA glyco-bond=--- sugar=-3- nts=3 GGG B.DG6,B.DG8,B.DG9 bulged-nts=1 C B.DC7
  strand#3  U DNA glyco-bond=--- sugar=--- nts=3 GGG B.DG11,B.DG12,B.DG13
  strand#4  U DNA glyco-bond=--- sugar=--- nts=3 GGG B.DG15,B.DG16,B.DG17
  loop#1 type=propeller strands=[#1,#2] nts=2 TT B.DT4,B.DT5
  loop#2 type=propeller strands=[#2,#3] nts=1 A B.DA10
  loop#3 type=propeller strands=[#3,#4] nts=1 T B.DT14