Detailed DSSR results for the G-quadruplex: PDB entry 5w77
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
- 5w77
- Class
- DNA-inhibitor
- Method
- NMR
- Summary
- Complex of DNA and compounds
- Reference
- Calabrese DR, Chen X, Leon EC, Gaikwad SM, Phyo Z, Hewitt WM, Alden S, Hilimire TA, He F, Michalowski AM, Simmons JK, Saunders LB, Zhang S, Connors D, Walters KJ, Mock BA, Schneekloth Jr JS (2018): "Chemical and structural studies provide a mechanistic basis for recognition of the MYC G-quadruplex." Nat Commun, 9, 4229. doi: 10.1038/s41467-018-06315-w.
- Abstract
- G-quadruplexes (G4s) are noncanonical DNA structures that frequently occur in the promoter regions of oncogenes, such as MYC, and regulate gene expression. Although G4s are attractive therapeutic targets, ligands capable of discriminating between different G4 structures are rare. Here, we describe DC-34, a small molecule that potently downregulates MYC transcription in cancer cells by a G4-dependent mechanism. Inhibition by DC-34 is significantly greater for MYC than other G4-driven genes. We use chemical, biophysical, biological, and structural studies to demonstrate a molecular rationale for the recognition of the MYC G4. We solve the structure of the MYC G4 in complex with DC-34 by NMR spectroscopy and illustrate specific contacts responsible for affinity and selectivity. Modification of DC-34 reveals features required for G4 affinity, biological activity, and validates the derived NMR structure. This work advances the design of quadruplex-interacting small molecules to control gene expression in therapeutic areas such as cancer.
- 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=-3-. groove=---- planarity=0.062 type=planar nts=4 GGGG A.DG7,A.DG11,A.DG16,A.DG20 2 glyco-bond=---- sugar=-3.- groove=---- planarity=0.047 type=planar nts=4 GGGG A.DG8,A.DG12,A.DG17,A.DG21 3 glyco-bond=---- sugar=---- groove=---- planarity=0.136 type=planar nts=4 GGGG A.DG9,A.DG13,A.DG18,A.DG22
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=-3-. groove=---- WC-->Major nts=4 GGGG A.DG7,A.DG11,A.DG16,A.DG20 2 glyco-bond=---- sugar=-3.- groove=---- WC-->Major nts=4 GGGG A.DG8,A.DG12,A.DG17,A.DG21 3 glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG9,A.DG13,A.DG18,A.DG22 step#1 pm(>>,forward) area=13.01 rise=3.21 twist=26.0 step#2 pm(>>,forward) area=12.50 rise=3.53 twist=28.3 strand#1 DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG7,A.DG8,A.DG9 strand#2 DNA glyco-bond=--- sugar=33- nts=3 GGG A.DG11,A.DG12,A.DG13 strand#3 DNA glyco-bond=--- sugar=-.- nts=3 GGG A.DG16,A.DG17,A.DG18 strand#4 DNA glyco-bond=--- sugar=.-- nts=3 GGG A.DG20,A.DG21,A.DG22 |
| 2 stacking diagrams | |
 |
1 glyco-bond=---- sugar=-3-. groove=---- WC-->Major nts=4 GGGG A.DG7,A.DG11,A.DG16,A.DG20 |
 |
2 glyco-bond=---- sugar=-3.- groove=---- WC-->Major nts=4 GGGG A.DG8,A.DG12,A.DG17,A.DG21 |
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=-3-. groove=---- WC-->Major nts=4 GGGG A.DG7,A.DG11,A.DG16,A.DG20 2 glyco-bond=---- sugar=-3.- groove=---- WC-->Major nts=4 GGGG A.DG8,A.DG12,A.DG17,A.DG21 3 glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG9,A.DG13,A.DG18,A.DG22 step#1 pm(>>,forward) area=13.01 rise=3.21 twist=26.0 step#2 pm(>>,forward) area=12.50 rise=3.53 twist=28.3 strand#1 U DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG7,A.DG8,A.DG9 strand#2 U DNA glyco-bond=--- sugar=33- nts=3 GGG A.DG11,A.DG12,A.DG13 strand#3 U DNA glyco-bond=--- sugar=-.- nts=3 GGG A.DG16,A.DG17,A.DG18 strand#4 U DNA glyco-bond=--- sugar=.-- nts=3 GGG A.DG20,A.DG21,A.DG22 loop#1 type=propeller strands=[#1,#2] nts=1 T A.DT10 loop#2 type=propeller strands=[#2,#3] nts=2 TA A.DT14,A.DA15 loop#3 type=propeller strands=[#3,#4] nts=1 T A.DT19 |