DSSR-curated G4 structure: PDB entry 6xrq

Summary information

PDB id: 6xrq
Class: RNA
Method: X-ray (1.21 Å)
Summary: Structural descriptions of ligand interactions to DNA and RNA quadruplexes folded from the non-coding region of pseudorabies virus
Reference: Zhang Y, Bux K, Attana F, Wei D, Haider S, Parkinson GN (2024): "Structural descriptions of ligand interactions to RNA quadruplexes folded from the non-coding region of Pseudorabies virus." Biochimie. doi: 10.1016/j.biochi.2024.06.003.
Abstract: To rationalise the binding of specific ligands to RNA-quadruplex we investigated several naphthalene diimide ligands that interact with the non-coding region of Pseudorabies virus (PRV). Herein we report on the x-ray structure of the naphthalene diimide ND11 with an RNA G-quadruplex putative forming sequence from rPRV. Consistent with previously observed rPRV sequence it assembles into a bimolecular RNA G-quadruplex consisting of a pair of two tetrads stacked 3' to 5'. We observe that ND11 interacts by binding on both the externally available 5' and 3' quartets. The CUC (loop 1) is structurally altered to enhance the 5' mode of interaction. These loop residues are shifted significantly to generate a new ligand binding pocket whereas the terminal A14 residue is lifted away from the RNA G-quadruplex tetrad plane to be restacked above the bound ND11 ligand NDI core. CD analysis of this family of NDI ligands shows consistency in the spectra between the different ligands in the presence of the rPRV RNA G-quadruplex motif, reflecting a common folded topology and mode of ligand interaction. FRET melt assay confirms the strong stabilising properties of the tetrasubstituted NDI compounds and the contributions length of the substituted groups have on melt temperatures.
G4 notes: 4 G-tetrads, 1 G4 helix, 2 G4 stems, 1 G4 coaxial stack, parallel(4+0), UUUU, coaxial interfaces: 3'/5'

Base-block schematics in six views

PyMOL session file	PDB file	View in 3Dmol.js

List of 4 G-tetrads

 1 glyco-bond=ssss sugar=3333 groove=---- planarity=0.179 type=other  nts=4 GGGG B.G1,A.G6,A.G1,B.G6
 2 glyco-bond=---- sugar=---- groove=---- planarity=0.143 type=planar nts=4 GGGG B.G2,B.G7,A.G2,A.G7
 3 glyco-bond=---- sugar=-3-3 groove=---- planarity=0.092 type=planar nts=4 GGGG B.G9,B.G12,A.G9,A.G12
 4 glyco-bond=---- sugar=---3 groove=---- planarity=0.226 type=bowl-2 nts=4 GGGG B.G10,B.G13,A.G10,A.G13

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, 4 G-tetrad layers, inter-molecular, with 2 stems

	1 glyco-bond=ssss sugar=3333 groove=---- Major-->WC nts=4 GGGG B.G1,A.G6,A.G1,B.G6 2* glyco-bond=---- sugar=---- groove=---- Major-->WC nts=4 GGGG B.G2,A.G7,A.G2,B.G7 3 glyco-bond=---- sugar=3-3- groove=---- WC-->Major nts=4 GGGG B.G12,A.G9,A.G12,B.G9 4 glyco-bond=---- sugar=--3- groove=---- WC-->Major nts=4 GGGG B.G13,A.G10,A.G13,B.G10 step#1 mp(<<,backward) area=5.15 rise=3.29 twist=-45.4 step#2 mm(<>,outward) area=28.06 rise=3.36 twist=-8.6 step#3 pm(>>,forward) area=9.70 rise=3.38 twist=30.6 strand#1 RNA glyco-bond=s--- sugar=3-3- nts=4 GGGG B.G1,B.G2,B.G12,B.G13 strand#2 RNA glyco-bond=s--- sugar=3--- nts=4 GGGG A.G6,A.G7,A.G9,A.G10 strand#3 RNA glyco-bond=s--- sugar=3-33 nts=4 GGGG A.G1,A.G2,A.G12,A.G13 strand#4 RNA glyco-bond=s--- sugar=3--- nts=4 GGGG B.G6,B.G7,B.G9,B.G10 Download PDB file Interactive view in 3Dmol.js
3 stacking diagrams
	1 glyco-bond=ssss sugar=3333 groove=---- Major-->WC nts=4 GGGG B.G1,A.G6,A.G1,B.G6 2* glyco-bond=---- sugar=---- groove=---- Major-->WC nts=4 GGGG B.G2,A.G7,A.G2,B.G7 step#1 mp(<<,backward) area=5.15 rise=3.29 twist=-45.4 Download PDB file Interactive view in 3Dmol.js
	2* glyco-bond=---- sugar=---- groove=---- Major-->WC nts=4 GGGG B.G2,A.G7,A.G2,B.G7 3 glyco-bond=---- sugar=3-3- groove=---- WC-->Major nts=4 GGGG B.G12,A.G9,A.G12,B.G9 step#2 mm(<>,outward) area=28.06 rise=3.36 twist=-8.6 Download PDB file Interactive view in 3Dmol.js
	3 glyco-bond=---- sugar=3-3- groove=---- WC-->Major nts=4 GGGG B.G12,A.G9,A.G12,B.G9 4 glyco-bond=---- sugar=--3- groove=---- WC-->Major nts=4 GGGG B.G13,A.G10,A.G13,B.G10 step#3 pm(>>,forward) area=9.70 rise=3.38 twist=30.6 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, 2 G-tetrad layers, 2 loops, inter-molecular, UUUU, parallel, parallel(4+0)

 1  glyco-bond=ssss sugar=3333 groove=---- Major-->WC nts=4 GGGG B.G1,A.G6,A.G1,B.G6
 2  glyco-bond=---- sugar=---- groove=---- Major-->WC nts=4 GGGG B.G2,A.G7,A.G2,B.G7
  step#1  mp(<<,backward) area=5.15  rise=3.29 twist=-45.4
  strand#1  U RNA glyco-bond=s- sugar=3- nts=2 GG B.G1,B.G2
  strand#2  U RNA glyco-bond=s- sugar=3- nts=2 GG A.G6,A.G7
  strand#3  U RNA glyco-bond=s- sugar=3- nts=2 GG A.G1,A.G2
  strand#4  U RNA glyco-bond=s- sugar=3- nts=2 GG B.G6,B.G7
  loop#1 type=propeller strands=[#1,#4] nts=3 CUC B.C3,B.U4,B.C5
  loop#2 type=propeller strands=[#3,#2] nts=3 CUC A.C3,A.U4,A.C5

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Stem#2, 2 G-tetrad layers, 2 loops, inter-molecular, UUUU, parallel, parallel(4+0)

 1  glyco-bond=---- sugar=-3-3 groove=---- WC-->Major nts=4 GGGG B.G9,B.G12,A.G9,A.G12
 2  glyco-bond=---- sugar=---3 groove=---- WC-->Major nts=4 GGGG B.G10,B.G13,A.G10,A.G13
  step#1  pm(>>,forward)  area=9.70  rise=3.38 twist=30.6
  strand#1  U RNA glyco-bond=-- sugar=-- nts=2 GG B.G9,B.G10
  strand#2  U RNA glyco-bond=-- sugar=3- nts=2 GG B.G12,B.G13
  strand#3  U RNA glyco-bond=-- sugar=-- nts=2 GG A.G9,A.G10
  strand#4  U RNA glyco-bond=-- sugar=33 nts=2 GG A.G12,A.G13
  loop#1 type=propeller strands=[#1,#2] nts=1 C B.C11
  loop#2 type=propeller strands=[#3,#4] nts=1 C A.C11