Detailed DSSR results for the G-quadruplex: PDB entry 8gp7
Created and maintained by Xiang-Jun Lu <xiangjun@x3dna.org>
Citation: Please cite the NAR'20 DSSR-PyMOL schematics paper and/or the NAR'15 DSSR method paper.
Summary information
- PDB id
- 8gp7
- Class
- DNA
- Method
- NMR
- Summary
- Structure of trioxacarcin a covalently bound to ret g4-DNA
- Reference
- Yin S, Lan W, Hou X, Liu Z, Xue H, Wang C, Tang GL, Cao C (2023): "Trioxacarcin A Interactions with G-Quadruplex DNA Reveal Its Potential New Targets as an Anticancer Agent." J.Med.Chem., 66, 6798-6810. doi: 10.1021/acs.jmedchem.3c00178.
- Abstract
- Trioxacarcin (TXN) A was reported to be an anticancer agent through alkylation of dsDNA. G-quadruplex DNA (G4-DNA) is frequently formed in the promoter regions of oncogenes and the ends of telomerase genes, considered as promising drug targets for anticancer therapy. There are no reports about TXN A interactions with G4-DNA. Here, we tested TXN A's interactions with several G4-DNA oligos with parallel, antiparallel, or hybrid folding, respectively. We demonstrated that TXN A preferred to alkylate one flexible guanine in the loops of parallel G4-DNA. The position of the alkylated guanine is in favor of interactions of G4-DNA with TXN A. The structure of TXN A covalently bound RET G4-DNA indicated that TXN A alkylation on RET G4-DNA stabilizes the G4-DNA conformation. These studies opened a new window of how TXN A interacted with G4-DNA, which might hint a new mode of its function as an anticancer agent.
- G4 notes
- 3 G-tetrads, 1 G4 helix, 1 G4 stem, 3(-P-P-P), parallel(4+0), UUUU
Base-block schematics in six views
List of 3 G-tetrads
1 glyco-bond=ssss sugar=3.3. groove=---- planarity=0.179 type=other nts=4 GGGG A.DG1,A.DG7,A.DG11,A.DG17 2 glyco-bond=---- sugar=333. groove=---- planarity=0.179 type=other nts=4 GGGG A.DG2,A.DG8,A.DG12,A.DG18 3 glyco-bond=---- sugar=3-33 groove=---- planarity=0.174 type=other nts=4 GGGG A.DG3,A.DG9,A.DG13,A.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, 3 G-tetrad layers, INTRA-molecular, with 1 stem
 |
1 glyco-bond=ssss sugar=3.3. groove=---- Major-->WC nts=4 GGGG A.DG1,A.DG7,A.DG11,A.DG17 2 glyco-bond=---- sugar=333. groove=---- WC-->Major nts=4 GGGG A.DG2,A.DG8,A.DG12,A.DG18 3 glyco-bond=---- sugar=3-33 groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG9,A.DG13,A.DG19 step#1 mm(<>,outward) area=12.29 rise=4.19 twist=19.7 step#2 pm(>>,forward) area=17.20 rise=4.03 twist=23.0 strand#1 DNA glyco-bond=s-- sugar=333 nts=3 GGG A.DG1,A.DG2,A.DG3 strand#2 DNA glyco-bond=s-- sugar=.3- nts=3 GGG A.DG7,A.DG8,A.DG9 strand#3 DNA glyco-bond=s-- sugar=333 nts=3 GGG A.DG11,A.DG12,A.DG13 strand#4 DNA glyco-bond=s-- sugar=..3 nts=3 GGG A.DG17,A.DG18,A.DG19 |
| 2 stacking diagrams | |
 |
1 glyco-bond=ssss sugar=3.3. groove=---- Major-->WC nts=4 GGGG A.DG1,A.DG7,A.DG11,A.DG17 |
 |
2 glyco-bond=---- sugar=333. groove=---- WC-->Major nts=4 GGGG A.DG2,A.DG8,A.DG12,A.DG18 |
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-tetrad layers, 3 loops, INTRA-molecular, UUUU, parallel, 3(-P-P-P), parallel(4+0)
 |
1 glyco-bond=ssss sugar=3.3. groove=---- Major-->WC nts=4 GGGG A.DG1,A.DG7,A.DG11,A.DG17 2 glyco-bond=---- sugar=333. groove=---- WC-->Major nts=4 GGGG A.DG2,A.DG8,A.DG12,A.DG18 3 glyco-bond=---- sugar=3-33 groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG9,A.DG13,A.DG19 step#1 mm(<>,outward) area=12.29 rise=4.19 twist=19.7 step#2 pm(>>,forward) area=17.20 rise=4.03 twist=23.0 strand#1 U DNA glyco-bond=s-- sugar=333 nts=3 GGG A.DG1,A.DG2,A.DG3 strand#2 U DNA glyco-bond=s-- sugar=.3- nts=3 GGG A.DG7,A.DG8,A.DG9 strand#3 U DNA glyco-bond=s-- sugar=333 nts=3 GGG A.DG11,A.DG12,A.DG13 strand#4 U DNA glyco-bond=s-- sugar=..3 nts=3 GGG A.DG17,A.DG18,A.DG19 loop#1 type=propeller strands=[#1,#2] nts=3 GCG A.DG4,A.DC5,A.DG6 loop#2 type=propeller strands=[#2,#3] nts=1 C A.DC10 loop#3 type=propeller strands=[#3,#4] nts=3 GCG A.DG14,A.DC15,A.DG16 |