DSSR-curated G4 structure: PDB entry 6p45

Summary information

PDB id: 6p45
Class: DNA
Method: X-ray (2.339 Å)
Summary: Crystal structure of the g-quadruplex formed by (tgggt)4 in complex with n-methylmesoporphryin ix
Reference: Lin LY, McCarthy S, Powell BM, Manurung Y, Xiang IM, Dean WL, Chaires B, Yatsunyk LA (2020): "Biophysical and X-ray structural studies of the (GGGTT)3GGG G-quadruplex in complex with N-methyl mesoporphyrin IX." Plos One, 15, e0241513. doi: 10.1371/journal.pone.0241513.
Abstract: The G-quadruplex (GQ) is a well-studied non-canonical DNA structure formed by G-rich sequences found at telomeres and gene promoters. Biological studies suggest that GQs may play roles in regulating gene expression, DNA replication, and DNA repair. Small molecule ligands were shown to alter GQ structure and stability and thereby serve as novel therapies, particularly against cancer. In this work, we investigate the interaction of a G-rich sequence, 5'-GGGTTGGGTTGGGTTGGG-3' (T1), with a water-soluble porphyrin, N-methyl mesoporphyrin IX (NMM) via biophysical and X-ray crystallographic studies. UV-vis and fluorescence titrations, as well as a Job plot, revealed a 1:1 binding stoichiometry with an impressively tight binding constant of 30-50 μM-1 and ΔG298 of -10.3 kcal/mol. Eight extended variants of T1 (named T2 -T9) were fully characterized and T7 was identified as a suitable candidate for crystallographic studies. We solved the crystal structures of the T1- and T7-NMM complexes at 2.39 and 2.34 Å resolution, respectively. Both complexes form a 5'-5' dimer of parallel GQs capped by NMM at the 3' G-quartet, supporting the 1:1 binding stoichiometry. Our work provides invaluable details about GQ-ligand binding interactions and informs the design of novel anticancer drugs that selectively recognize specific GQs and modulate their stability for therapeutic purposes.
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'

Base-block schematics in six views

PyMOL session file	PDB file	View in 3Dmol.js

List of 6 G-tetrads

 1 glyco-bond=---- sugar=---- groove=---- planarity=0.070 type=planar nts=4 GGGG A.DG2,A.DG7,A.DG12,A.DG17
 2 glyco-bond=---- sugar=---- groove=---- planarity=0.171 type=other  nts=4 GGGG A.DG3,A.DG8,A.DG13,A.DG18
 3 glyco-bond=---- sugar=---- groove=---- planarity=0.360 type=bowl   nts=4 GGGG A.DG4,A.DG9,A.DG14,A.DG19
 4 glyco-bond=---- sugar=---- groove=---- planarity=0.064 type=planar nts=4 GGGG B.DG2,B.DG7,B.DG12,B.DG17
 5 glyco-bond=---- sugar=---- groove=---- planarity=0.171 type=other  nts=4 GGGG B.DG3,B.DG8,B.DG13,B.DG18
 6 glyco-bond=---- sugar=---- groove=---- planarity=0.372 type=bowl   nts=4 GGGG B.DG4,B.DG9,B.DG14,B.DG19

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-tetrad layers, inter-molecular, with 2 stems

	1 glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG4,A.DG9,A.DG14,A.DG19 2 glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG8,A.DG13,A.DG18 3* glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG2,A.DG7,A.DG12,A.DG17 4 glyco-bond=---- sugar=---- groove=---- Major-->WC nts=4 GGGG B.DG17,B.DG12,B.DG7,B.DG2 5 glyco-bond=---- sugar=---- groove=---- Major-->WC nts=4 GGGG B.DG18,B.DG13,B.DG8,B.DG3 6 glyco-bond=---- sugar=---- groove=---- Major-->WC nts=4 GGGG B.DG19,B.DG14,B.DG9,B.DG4 step#1 mp(<<,backward) area=9.16 rise=3.47 twist=28.8 step#2 mp(<<,backward) area=11.41 rise=3.50 twist=28.0 step#3 mm(<>,outward) area=27.69 rise=3.36 twist=-9.2 step#4 pm(>>,forward) area=11.00 rise=3.44 twist=28.3 step#5 pm(>>,forward) area=9.59 rise=3.51 twist=27.5 strand#1 DNA glyco-bond=------ sugar=------ nts=6 GGGGGG A.DG4,A.DG3,A.DG2,B.DG17,B.DG18,B.DG19 strand#2 DNA glyco-bond=------ sugar=------ nts=6 GGGGGG A.DG9,A.DG8,A.DG7,B.DG12,B.DG13,B.DG14 strand#3 DNA glyco-bond=------ sugar=------ nts=6 GGGGGG A.DG14,A.DG13,A.DG12,B.DG7,B.DG8,B.DG9 strand#4 DNA glyco-bond=------ sugar=------ nts=6 GGGGGG A.DG19,A.DG18,A.DG17,B.DG2,B.DG3,B.DG4 Download PDB file Interactive view in 3Dmol.js
5 stacking diagrams
	1 glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG4,A.DG9,A.DG14,A.DG19 2 glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG8,A.DG13,A.DG18 step#1 mp(<<,backward) area=9.16 rise=3.47 twist=28.8 Download PDB file Interactive view in 3Dmol.js
	2 glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG8,A.DG13,A.DG18 3* glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG2,A.DG7,A.DG12,A.DG17 step#2 mp(<<,backward) area=11.41 rise=3.50 twist=28.0 Download PDB file Interactive view in 3Dmol.js
	3* glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG2,A.DG7,A.DG12,A.DG17 4 glyco-bond=---- sugar=---- groove=---- Major-->WC nts=4 GGGG B.DG17,B.DG12,B.DG7,B.DG2 step#3 mm(<>,outward) area=27.69 rise=3.36 twist=-9.2 Download PDB file Interactive view in 3Dmol.js
	4 glyco-bond=---- sugar=---- groove=---- Major-->WC nts=4 GGGG B.DG17,B.DG12,B.DG7,B.DG2 5 glyco-bond=---- sugar=---- groove=---- Major-->WC nts=4 GGGG B.DG18,B.DG13,B.DG8,B.DG3 step#4 pm(>>,forward) area=11.00 rise=3.44 twist=28.3 Download PDB file Interactive view in 3Dmol.js
	5 glyco-bond=---- sugar=---- groove=---- Major-->WC nts=4 GGGG B.DG18,B.DG13,B.DG8,B.DG3 6 glyco-bond=---- sugar=---- groove=---- Major-->WC nts=4 GGGG B.DG19,B.DG14,B.DG9,B.DG4 step#5 pm(>>,forward) area=9.59 rise=3.51 twist=27.5 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-tetrad layers, 3 loops, INTRA-molecular, UUUU, parallel, 3(-P-P-P), parallel(4+0)

 1  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG2,A.DG7,A.DG12,A.DG17
 2  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG8,A.DG13,A.DG18
 3  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG4,A.DG9,A.DG14,A.DG19
  step#1  pm(>>,forward)  area=11.41 rise=3.50 twist=28.0
  step#2  pm(>>,forward)  area=9.16  rise=3.47 twist=28.8
  strand#1  U DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG2,A.DG3,A.DG4
  strand#2  U DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG7,A.DG8,A.DG9
  strand#3  U DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG12,A.DG13,A.DG14
  strand#4  U DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG17,A.DG18,A.DG19
  loop#1 type=propeller strands=[#1,#2] nts=2 TT A.DT5,A.DT6
  loop#2 type=propeller strands=[#2,#3] nts=2 TT A.DT10,A.DT11
  loop#3 type=propeller strands=[#3,#4] nts=2 TT A.DT15,A.DT16

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

 1  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG B.DG2,B.DG7,B.DG12,B.DG17
 2  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG B.DG3,B.DG8,B.DG13,B.DG18
 3  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG B.DG4,B.DG9,B.DG14,B.DG19
  step#1  pm(>>,forward)  area=11.00 rise=3.44 twist=28.3
  step#2  pm(>>,forward)  area=9.59  rise=3.51 twist=27.5
  strand#1  U DNA glyco-bond=--- sugar=--- nts=3 GGG B.DG2,B.DG3,B.DG4
  strand#2  U DNA glyco-bond=--- sugar=--- nts=3 GGG B.DG7,B.DG8,B.DG9
  strand#3  U DNA glyco-bond=--- sugar=--- nts=3 GGG B.DG12,B.DG13,B.DG14
  strand#4  U DNA glyco-bond=--- sugar=--- nts=3 GGG B.DG17,B.DG18,B.DG19
  loop#1 type=propeller strands=[#1,#2] nts=2 TT B.DT5,B.DT6
  loop#2 type=propeller strands=[#2,#3] nts=2 TT B.DT10,B.DT11
  loop#3 type=propeller strands=[#3,#4] nts=2 TT B.DT15,B.DT16