Detailed DSSR results for the G-quadruplex: PDB entry 7sxp
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
- 7sxp
- Class
- RNA
- Method
- X-ray (2.9 Å)
- Summary
- G-quadruplex structure formed in the nras mrna with a g8u substitution
- Reference
- Balaratnam S, Torrey ZR, Calabrese DR, Banco MT, Yazdani K, Liang X, Fullenkamp CR, Seshadri S, Holewinski RJ, Andresson T, Ferre-D'Amare AR, Incarnato D, Schneekloth Jr JS (2023): "Investigating the NRAS 5' UTR as a target for small molecules." Cell Chem Biol, 30, 643-657.e8. doi: 10.1016/j.chembiol.2023.05.004.
- Abstract
- Neuroblastoma RAS (NRAS) is an oncogene that is deregulated and highly mutated in cancers including melanomas and acute myeloid leukemias. The 5' untranslated region (UTR) (5' UTR) of the NRAS mRNA contains a G-quadruplex (G4) that regulates translation. Here we report a novel class of small molecule that binds to the G4 structure located in the 5' UTR of the NRAS mRNA. We used a small molecule microarray screen to identify molecules that selectively bind to the NRAS-G4 with submicromolar affinity. One compound inhibits the translation of NRAS in vitro but showed only moderate effects on the NRAS levels in cellulo. Rapid Amplification of cDNA Ends and RT-PCR analysis revealed that the predominant NRAS transcript does not possess the G4 structure. Thus, although NRAS transcripts lack a G4 in many cell lines the concept of targeting folded regions within 5' UTRs to control translation remains a highly attractive strategy.
- G4 notes
- 3 G-tetrads, 1 G4 helix, 1 G4 stem, 3(-P-P), parallel(4+0), UUUU
Base-block schematics in six views
List of 3 G-tetrads
1 glyco-bond=---- sugar=33-- groove=---- planarity=0.131 type=planar nts=4 GGGG A.G4,A.G9,A.G13,A.G19 2 glyco-bond=---- sugar=3333 groove=---- planarity=0.131 type=planar nts=4 GGGG A.G5,A.G10,A.G14,A.G20 3 glyco-bond=---- sugar=---- groove=---- planarity=0.429 type=bowl nts=4 GGGG A.G6,A.G11,A.G15,A.G21
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=33-- groove=---- WC-->Major nts=4 GGGG A.G4,A.G9,A.G13,A.G19 2 glyco-bond=---- sugar=3333 groove=---- WC-->Major nts=4 GGGG A.G5,A.G10,A.G14,A.G20 3 glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.G6,A.G11,A.G15,A.G21 step#1 pm(>>,forward) area=7.75 rise=3.21 twist=34.6 step#2 pm(>>,forward) area=14.80 rise=3.69 twist=23.7 strand#1 RNA glyco-bond=--- sugar=33- nts=3 GGG A.G4,A.G5,A.G6 strand#2 RNA glyco-bond=--- sugar=33- nts=3 GGG A.G9,A.G10,A.G11 strand#3 RNA glyco-bond=--- sugar=-3- nts=3 GGG A.G13,A.G14,A.G15 strand#4 RNA glyco-bond=--- sugar=-3- nts=3 GGG A.G19,A.G20,A.G21 |
| 2 stacking diagrams | |
 |
1 glyco-bond=---- sugar=33-- groove=---- WC-->Major nts=4 GGGG A.G4,A.G9,A.G13,A.G19 |
 |
2 glyco-bond=---- sugar=3333 groove=---- WC-->Major nts=4 GGGG A.G5,A.G10,A.G14,A.G20 |
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, 2 loops, INTRA-molecular, UUUU, parallel, 3(-P-P), parallel(4+0)
 |
1 glyco-bond=---- sugar=33-- groove=---- WC-->Major nts=4 GGGG A.G4,A.G9,A.G13,A.G19 2 glyco-bond=---- sugar=3333 groove=---- WC-->Major nts=4 GGGG A.G5,A.G10,A.G14,A.G20 3 glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.G6,A.G11,A.G15,A.G21 step#1 pm(>>,forward) area=7.75 rise=3.21 twist=34.6 step#2 pm(>>,forward) area=14.80 rise=3.69 twist=23.7 strand#1 U RNA glyco-bond=--- sugar=33- nts=3 GGG A.G4,A.G5,A.G6 strand#2 U RNA glyco-bond=--- sugar=33- nts=3 GGG A.G9,A.G10,A.G11 strand#3 U RNA glyco-bond=--- sugar=-3- nts=3 GGG A.G13,A.G14,A.G15 strand#4 U RNA glyco-bond=--- sugar=-3- nts=3 GGG A.G19,A.G20,A.G21 loop#1 type=propeller strands=[#2,#3] nts=1 C A.C12 loop#2 type=propeller strands=[#3,#4] nts=3 UCU A.U16,A.C17,A.U18 |