DSSR-enabled G4 identification/annotation: PDB entry 8t8t
Summary information and primary citation
- PDB-id
- 8t8t
- Class
- DNA
- Method
- X-ray (1.62 Å)
- Summary
- Crystal structure of tet25 in complex with pydh2 ligand in p212121 space group
- Reference
- Martin KN, Lam G, Reznichenko O, Brunner KE, Zdilla MJ, McCarthy SE, Granzhan A, Yatsunyk LA (2025): "Conformational Change in a Four-Tetrad DNA G-Quadruplex upon Intercalation of a Small-Molecule Ligand PyDH2." Angew.Chem.Int.Ed.Engl., 64, e202501443. doi: 10.1002/anie.202501443.
- Abstract
- G-quadruplexes (G4s) are non-canonical DNA structures implicated in a number of biological processes. Small-molecule ligands can alter stability and folding of G4s, which can potentially be exploited for therapeutic purposes. In this work, we investigate the interaction of telomeric DNA fragment from Tetrahymena thermophila (TET25, 5'-G(TTGGGG)<sub>4-</sub>3') with a G4 ligand PyDH2 belonging to the bisquinolinium family. When alone, TET25 adopts a mixture of three conformations, with the most abundant being a four-tetrad hybrid G4. In the presence of PyDH2, surprisingly, TET25 folds into an antiparallel chair G4, with PyDH2 intercalated between G-tetrads 2 and 3, according to our crystal structure. The structure represents the second example, and the first crystallographic evidence, of ligand intercalation into a G4. In solution, the interaction of PyDH2 and TET25 leads to a number of complexes differing by G4 topology and binding stoichiometry, strong stabilization of G4 (∆T<sub>m</sub> = 12.4 °C in the presence of one equiv. of PyDH2) and large hysteresis of ∼10 °C, suggesting that ligand binding and G4 folding processes are complex.
- G4 notes
- 4 G-tetrads, 1 G4 helix, 1 G4 stem, UDUD, anti-parallel:chair, 2+2, 4(+Ln+Lw+Ln)
Cartoon-block schematics in six views (download the tarball)
List of 4 G-tetrads
1 glyco-bond=s-s- sugar=-.-- groove=wnwn planarity=0.457 type=other O+ nts=4 GGGG 1:A.DG4,1:A.DG25,1:A.DG16,1:A.DG13 2 glyco-bond=-s-s sugar=---- groove=wnwn planarity=0.447 type=other O- nts=4 GGGG 1:A.DG5,1:A.DG24,1:A.DG17,1:A.DG12 3 glyco-bond=s-s- sugar=---- groove=wnwn planarity=0.423 type=other O+ nts=4 GGGG 1:A.DG6,1:A.DG23,1:A.DG18,1:A.DG11 4 glyco-bond=-s-s sugar=-.-- groove=wnwn planarity=0.480 type=bowl-2 O- nts=4 GGGG 1:A.DG7,1:A.DG22,1:A.DG19,1:A.DG10
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-tetrads, INTRA-molecular, with 1 stem
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1 glyco-bond=s-s- sugar=-.-- groove=wnwn Major-->WC O+ nts=4 GGGG 1:A.DG4,1:A.DG25,1:A.DG16,1:A.DG13 2 glyco-bond=-s-s sugar=---- groove=wnwn WC-->Major O- nts=4 GGGG 1:A.DG5,1:A.DG24,1:A.DG17,1:A.DG12 3 glyco-bond=s-s- sugar=---- groove=wnwn Major-->WC O+ nts=4 GGGG 1:A.DG6,1:A.DG23,1:A.DG18,1:A.DG11 4 glyco-bond=-s-s sugar=-.-- groove=wnwn WC-->Major O- nts=4 GGGG 1:A.DG7,1:A.DG22,1:A.DG19,1:A.DG10 step#1 mm(<>,outward) area=15.96 rise=3.51 twist=15.5 step#2 pp(><,inward) area=0.00 rise=6.61 twist=22.6 step#3 mm(<>,outward) area=19.17 rise=3.44 twist=12.9 strand#1 DNA glyco-bond=s-s- sugar=---- nts=4 GGGG 1:A.DG4,1:A.DG5,1:A.DG6,1:A.DG7 strand#2 DNA glyco-bond=-s-s sugar=.--. nts=4 GGGG 1:A.DG25,1:A.DG24,1:A.DG23,1:A.DG22 strand#3 DNA glyco-bond=s-s- sugar=---- nts=4 GGGG 1:A.DG16,1:A.DG17,1:A.DG18,1:A.DG19 strand#4 DNA glyco-bond=-s-s sugar=---- nts=4 GGGG 1:A.DG13,1:A.DG12,1:A.DG11,1:A.DG10 |
| 3 stacking diagrams | |
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1 glyco-bond=s-s- sugar=-.-- groove=wnwn Major-->WC O+ nts=4 GGGG 1:A.DG4,1:A.DG25,1:A.DG16,1:A.DG13 |
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2 glyco-bond=-s-s sugar=---- groove=wnwn WC-->Major O- nts=4 GGGG 1:A.DG5,1:A.DG24,1:A.DG17,1:A.DG12 |
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3 glyco-bond=s-s- sugar=---- groove=wnwn Major-->WC O+ nts=4 GGGG 1:A.DG6,1:A.DG23,1:A.DG18,1:A.DG11 |
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, 4 G-tetrads, 3 loops, INTRA-molecular, UDUD, anti-parallel:chair, 2+2, 4(+Ln+Lw+Ln)
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1 glyco-bond=s-s- sugar=-.-- groove=wnwn Major-->WC O+ nts=4 GGGG 1:A.DG4,1:A.DG25,1:A.DG16,1:A.DG13 2 glyco-bond=-s-s sugar=---- groove=wnwn WC-->Major O- nts=4 GGGG 1:A.DG5,1:A.DG24,1:A.DG17,1:A.DG12 3 glyco-bond=s-s- sugar=---- groove=wnwn Major-->WC O+ nts=4 GGGG 1:A.DG6,1:A.DG23,1:A.DG18,1:A.DG11 4 glyco-bond=-s-s sugar=-.-- groove=wnwn WC-->Major O- nts=4 GGGG 1:A.DG7,1:A.DG22,1:A.DG19,1:A.DG10 step#1 mm(<>,outward) area=15.96 rise=3.51 twist=15.5 step#2 pp(><,inward) area=0.00 rise=6.61 twist=22.6 step#3 mm(<>,outward) area=19.17 rise=3.44 twist=12.9 strand#1 U DNA glyco-bond=s-s- sugar=---- nts=4 GGGG 1:A.DG4,1:A.DG5,1:A.DG6,1:A.DG7 strand#2 D DNA glyco-bond=-s-s sugar=.--. nts=4 GGGG 1:A.DG25,1:A.DG24,1:A.DG23,1:A.DG22 strand#3 U DNA glyco-bond=s-s- sugar=---- nts=4 GGGG 1:A.DG16,1:A.DG17,1:A.DG18,1:A.DG19 strand#4 D DNA glyco-bond=-s-s sugar=---- nts=4 GGGG 1:A.DG13,1:A.DG12,1:A.DG11,1:A.DG10 loop#1 type=lateral strands=[#1,#4] nts=2 TT 1:A.DT8,1:A.DT9 loop#2 type=lateral strands=[#4,#3] nts=2 TT 1:A.DT14,1:A.DT15 loop#3 type=lateral strands=[#3,#2] nts=2 TT 1:A.DT20,1:A.DT21 |