DSSR-enabled G4 identification/annotation: PDB entry 6au4
Summary information and primary citation
- PDB-id
- 6au4
- Class
- DNA
- Method
- X-ray (2.35 Å)
- Summary
- Crystal structure of the major quadruplex formed in the human c-myc promoter
- Reference
- Stump S, Mou TC, Sprang SR, Natale NR, Beall HD (2018): "Crystal structure of the major quadruplex formed in the promoter region of the human c-MYC oncogene." PLoS ONE, 13, e0205584. doi: 10.1371/journal.pone.0205584.
- Abstract
- The c-MYC oncogene mediates multiple tumor cell survival pathways and is dysregulated or overexpressed in the majority of human cancers. The NHE III1 region of the c-MYC promoter forms a DNA quadruplex. Stabilization of this structure with small molecules has been shown to reduce expression of c-MYC, and targeting the c-MYC quadruplex has become an emerging strategy for development of antitumor compounds. Previous solution NMR studies of the c-MYC quadruplex have assigned the major conformer and topology of this important target, however, regions outside the G-quartet core were not as well-defined. Here, we report a high-resolution crystal structure (2.35 Å) of the major quadruplex formed in the NHE III1 region of the c-MYC promoter. The crystal structure is in general agreement with the solution NMR structure, however, key differences are observed in the position of nucleotides outside the G-quartet core. The crystal structure provides an alternative model that, along with comparisons to other reported quadruplex crystal structures, will be important to the rational design of selective compounds. This work will aid in development of ligands to target the c-MYC promoter quadruplex with the goal of creating novel anticancer therapies.
- G4 notes
- 6 G-tetrads, 2 G4 helices, 2 G4 stems, UUUU, parallel, 4+0, 3(-P-P-P)
Cartoon-block schematics in six views (download the tarball)
List of 6 G-tetrads
1 glyco-bond=---- sugar=---- groove=---- planarity=0.043 type=planar O+ nts=4 GGGG A.DG4,A.DG8,A.DG13,A.DG17 2 glyco-bond=---- sugar=--.- groove=---- planarity=0.130 type=planar O+ nts=4 GGGG A.DG5,A.DG9,A.DG14,A.DG18 3 glyco-bond=---- sugar=---- groove=---- planarity=0.197 type=bowl O+ nts=4 GGGG A.DG6,A.DG10,A.DG15,A.DG19 4 glyco-bond=---- sugar=3--- groove=---- planarity=0.074 type=planar O+ nts=4 GGGG B.DG4,B.DG8,B.DG13,B.DG17 5 glyco-bond=---- sugar=---- groove=---- planarity=0.140 type=planar O+ nts=4 GGGG B.DG5,B.DG9,B.DG14,B.DG18 6 glyco-bond=---- sugar=---- groove=---- planarity=0.249 type=bowl O+ nts=4 GGGG B.DG6,B.DG10,B.DG15,B.DG19
List of 2 G4-helices
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-tetrads, INTRA-molecular, with 1 stem
|
1 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG4,A.DG8,A.DG13,A.DG17 2 glyco-bond=---- sugar=--.- groove=---- WC-->Major O+ nts=4 GGGG A.DG5,A.DG9,A.DG14,A.DG18 3 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG6,A.DG10,A.DG15,A.DG19 step#1 pm(>>,forward) area=10.75 rise=3.36 twist=30.5 step#2 pm(>>,forward) area=10.96 rise=3.34 twist=29.0 strand#1 DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG4,A.DG5,A.DG6 strand#2 DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG8,A.DG9,A.DG10 strand#3 DNA glyco-bond=--- sugar=-.- nts=3 GGG A.DG13,A.DG14,A.DG15 strand#4 DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG17,A.DG18,A.DG19 |
| 2 stacking diagrams | |
|
1 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG4,A.DG8,A.DG13,A.DG17 |
|
2 glyco-bond=---- sugar=--.- groove=---- WC-->Major O+ nts=4 GGGG A.DG5,A.DG9,A.DG14,A.DG18 |
Helix#2, 3 G-tetrads, INTRA-molecular, with 1 stem
|
1 glyco-bond=---- sugar=3--- groove=---- WC-->Major O+ nts=4 GGGG B.DG4,B.DG8,B.DG13,B.DG17 2 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG B.DG5,B.DG9,B.DG14,B.DG18 3 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG B.DG6,B.DG10,B.DG15,B.DG19 step#1 pm(>>,forward) area=10.11 rise=3.37 twist=30.8 step#2 pm(>>,forward) area=11.50 rise=3.47 twist=28.9 strand#1 DNA glyco-bond=--- sugar=3-- nts=3 GGG B.DG4,B.DG5,B.DG6 strand#2 DNA glyco-bond=--- sugar=--- nts=3 GGG B.DG8,B.DG9,B.DG10 strand#3 DNA glyco-bond=--- sugar=--- nts=3 GGG B.DG13,B.DG14,B.DG15 strand#4 DNA glyco-bond=--- sugar=--- nts=3 GGG B.DG17,B.DG18,B.DG19 |
| 2 stacking diagrams | |
|
1 glyco-bond=---- sugar=3--- groove=---- WC-->Major O+ nts=4 GGGG B.DG4,B.DG8,B.DG13,B.DG17 |
|
2 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG B.DG5,B.DG9,B.DG14,B.DG18 |
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-tetrads, 3 loops, INTRA-molecular, UUUU, parallel, 4+0, 3(-P-P-P)
|
1 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG4,A.DG8,A.DG13,A.DG17 2 glyco-bond=---- sugar=--.- groove=---- WC-->Major O+ nts=4 GGGG A.DG5,A.DG9,A.DG14,A.DG18 3 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG6,A.DG10,A.DG15,A.DG19 step#1 pm(>>,forward) area=10.75 rise=3.36 twist=30.5 step#2 pm(>>,forward) area=10.96 rise=3.34 twist=29.0 strand#1 U DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG4,A.DG5,A.DG6 strand#2 U DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG8,A.DG9,A.DG10 strand#3 U DNA glyco-bond=--- sugar=-.- nts=3 GGG A.DG13,A.DG14,A.DG15 strand#4 U DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG17,A.DG18,A.DG19 loop#1 type=propeller strands=[#1,#2] nts=1 T A.DT7 loop#2 type=propeller strands=[#2,#3] nts=2 TA A.DT11,A.DA12 loop#3 type=propeller strands=[#3,#4] nts=1 T A.DT16 |
Stem#2, 3 G-tetrads, 3 loops, INTRA-molecular, UUUU, parallel, 4+0, 3(-P-P-P)
|
1 glyco-bond=---- sugar=3--- groove=---- WC-->Major O+ nts=4 GGGG B.DG4,B.DG8,B.DG13,B.DG17 2 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG B.DG5,B.DG9,B.DG14,B.DG18 3 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG B.DG6,B.DG10,B.DG15,B.DG19 step#1 pm(>>,forward) area=10.11 rise=3.37 twist=30.8 step#2 pm(>>,forward) area=11.50 rise=3.47 twist=28.9 strand#1 U DNA glyco-bond=--- sugar=3-- nts=3 GGG B.DG4,B.DG5,B.DG6 strand#2 U DNA glyco-bond=--- sugar=--- nts=3 GGG B.DG8,B.DG9,B.DG10 strand#3 U DNA glyco-bond=--- sugar=--- nts=3 GGG B.DG13,B.DG14,B.DG15 strand#4 U DNA glyco-bond=--- sugar=--- nts=3 GGG B.DG17,B.DG18,B.DG19 loop#1 type=propeller strands=[#1,#2] nts=1 T B.DT7 loop#2 type=propeller strands=[#2,#3] nts=2 TA B.DT11,B.DA12 loop#3 type=propeller strands=[#3,#4] nts=1 T B.DT16 |