Summary information [schematics · tetrads · helices · stems · costacks · homepage]

PDB-id
6t2g
Class
DNA
Method
NMR
Summary
NMR structure of kras32r g25t conformer G-quadruplex within kras promoter region
Reference
Marquevielle, J., Robert, C., Lagrabette, O., Wahid, M., Bourdoncle, A., Xodo, L.E., Mergny, J.L., Salgado, G.F.: (2020) "Structure of two G-quadruplexes in equilibrium in the KRAS promoter." Nucleic Acids Res.
Abstract
KRAS is one of the most mutated oncogenes and still considered an undruggable target. An alternative strategy would consist in targeting its gene rather than the protein, specifically the formation of G-quadruplexes (G4) in its promoter. G4 are secondary structures implicated in biological processes, which can be formed among G-rich DNA (or RNA) sequences. Here we have studied the major conformations of the commonly known KRASĀ 32R, or simply 32R, a 32 residue sequence within the KRAS Nuclease Hypersensitive Element (NHE) region. We have determined the structure of the two major stable conformers that 32R can adopt and which display slow equilibrium (>ms) with each other. By using different biophysical methods, we found that the nucleotides G9, G25, G28 and G32 are particularly implicated in the exchange between these two conformations. We also showed that a triad at the 3' end further stabilizes one of the G4 conformations, while the second conformer remains more flexible and less stable.
G4 notes
2 G-tetrads

Base-block schematics in six views [summary · tetrads · helices · stems · costacks · homepage]

PyMOL session file PDB file View in 3Dmol.js

List of 2 G-tetrads [summary · schematics · helices · stems · costacks · homepage]

 1 glyco-bond=---- groove=---- planarity=0.448 type=bowl   nts=4 GGGG A.DG2,A.DG6,A.DG11,A.DG26
 2 glyco-bond=---- groove=---- planarity=0.655 type=saddle nts=4 GGGG A.DG4,A.DG9,A.DG13,A.DG28

List of 0 G4-helices [summary · schematics · tetrads · stems · costacks · homepage]

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.

List of 0 G4-stems [summary · schematics · tetrads · helices · costacks · homepage]

In DSSR, a G4-stem is defined as a G4-helix with backbone connectivity. Bulges are also allowed along each of the four strands.

List of 0 G4 coaxial stacks [summary · schematics · tetrads · helices · stems · homepage]

List of 6 non-stem G4-loops (including the two closing Gs)

 1 type=lateral   helix=#-1 nts=5 GGGCG A.DG2,A.DG3,A.DG4,A.DC5,A.DG6
 2 type=lateral   helix=#-2 nts=6 GCGGTG A.DG4,A.DC5,A.DG6,A.DG7,A.DT8,A.DG9
 3 type=lateral   helix=#-1 nts=6 GGTGTG A.DG6,A.DG7,A.DT8,A.DG9,A.DT10,A.DG11
 4 type=lateral   helix=#-2 nts=5 GTGGG A.DG9,A.DT10,A.DG11,A.DG12,A.DG13
 5 type=lateral   helix=#-1 nts=16 GGGAAGAGGGAAGATG A.DG11,A.DG12,A.DG13,A.DA14,A.DA15,A.DG16,A.DA17,A.DG18,A.DG19,A.DG20,A.DA21,A.DA22,A.DG23,A.DA24,A.DT25,A.DG26
 6 type=lateral   helix=#-2 nts=16 GAAGAGGGAAGATGGG A.DG13,A.DA14,A.DA15,A.DG16,A.DA17,A.DG18,A.DG19,A.DG20,A.DA21,A.DA22,A.DG23,A.DA24,A.DT25,A.DG26,A.DG27,A.DG28