Detailed DSSR results for the G-quadruplex: PDB entry 6lnz
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
- 6lnz
- Class
- DNA
- Method
- NMR
- Summary
- NMR solution structure of vegf g-quadruplex bound a non-planar cyclometalated-carbene platinum(ii) complex
- Reference
- Zhu BC, He J, Liu W, Xia XY, Liu LY, Liang BB, Yao HG, Liu B, Ji LN, Mao ZW (2021): "Selectivity and Targeting of G-Quadruplex Binders Activated by Adaptive Binding and Controlled by Chemical Kinetics." Angew.Chem.Int.Ed.Engl., 60, 15340-15343. doi: 10.1002/anie.202104624.
- Abstract
- G-quadruplexes (G4s) are prevalent in oncogenes and are potential antitumor drug targets. However, binding selectivity of compounds to G4s still faces challenges. Herein, we report a platinum(II) complex (Pt1), whose affinity to G4-DNA is activated by adaptive binding and selectivity controlled by binding kinetics. The resolved structure of Pt1/VEGF-G4 (a promoter G4) shows that Pt1 matches 3'-G-tetrad of VEGF-G4 through Cl- -dissociation and loop rearrangement of VEGF-G4. Binding rate constants are determined by coordination bond breakage/formation, correlating fully with affinities. The selective rate-determining binding step, Cl- -dissociation upon G4-binding, is 2-3 orders of magnitude higher than dsDNA. Pt1 potently targets G4 in living cells, effectively represses VEGF expression, and inhibits vascular growth in zebrafish. We show adaptive G4-binding activation and controlled by kinetics, providing a complementary design principle for compounds targeting G4 or similar biomolecules.
- 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=---- sugar=.... groove=---- planarity=0.139 type=planar nts=4 GGGG A.DG3,A.DG7,A.DG14,A.DG18 2 glyco-bond=---- sugar=.... groove=---- planarity=0.091 type=planar nts=4 GGGG A.DG4,A.DG8,A.DG15,A.DG19 3 glyco-bond=---- sugar=..-. groove=---- planarity=0.116 type=planar nts=4 GGGG A.DG5,A.DG9,A.DG16,A.DG20
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=---- sugar=.... groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG7,A.DG14,A.DG18 2 glyco-bond=---- sugar=.... groove=---- WC-->Major nts=4 GGGG A.DG4,A.DG8,A.DG15,A.DG19 3 glyco-bond=---- sugar=..-. groove=---- WC-->Major nts=4 GGGG A.DG5,A.DG9,A.DG16,A.DG20 step#1 pm(>>,forward) area=16.65 rise=3.77 twist=25.3 step#2 pm(>>,forward) area=12.12 rise=3.75 twist=27.6 strand#1 DNA glyco-bond=--- sugar=... nts=3 GGG A.DG3,A.DG4,A.DG5 strand#2 DNA glyco-bond=--- sugar=... nts=3 GGG A.DG7,A.DG8,A.DG9 strand#3 DNA glyco-bond=--- sugar=..- nts=3 GGG A.DG14,A.DG15,A.DG16 strand#4 DNA glyco-bond=--- sugar=... nts=3 GGG A.DG18,A.DG19,A.DG20 |
| 2 stacking diagrams | |
 |
1 glyco-bond=---- sugar=.... groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG7,A.DG14,A.DG18 |
 |
2 glyco-bond=---- sugar=.... groove=---- WC-->Major nts=4 GGGG A.DG4,A.DG8,A.DG15,A.DG19 |
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=---- sugar=.... groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG7,A.DG14,A.DG18 2 glyco-bond=---- sugar=.... groove=---- WC-->Major nts=4 GGGG A.DG4,A.DG8,A.DG15,A.DG19 3 glyco-bond=---- sugar=..-. groove=---- WC-->Major nts=4 GGGG A.DG5,A.DG9,A.DG16,A.DG20 step#1 pm(>>,forward) area=16.65 rise=3.77 twist=25.3 step#2 pm(>>,forward) area=12.12 rise=3.75 twist=27.6 strand#1 U DNA glyco-bond=--- sugar=... nts=3 GGG A.DG3,A.DG4,A.DG5 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.DG14,A.DG15,A.DG16 strand#4 U DNA glyco-bond=--- sugar=... nts=3 GGG A.DG18,A.DG19,A.DG20 loop#1 type=propeller strands=[#1,#2] nts=1 C A.DC6 loop#2 type=propeller strands=[#2,#3] nts=4 CCTT A.DC10,A.DC11,A.DT12,A.DT13 loop#3 type=propeller strands=[#3,#4] nts=1 C A.DC17 |