Summary information and primary citation

PDB-id
6suu
Class
DNA
Method
NMR
Summary
NMR structure of kras32r g9t conformer g-quadruplex within kras promoter region
Reference
Marquevielle J, Robert C, Lagrabette O, Wahid M, Bourdoncle A, Xodo LE, Mergny JL, Salgado GF (2020): "Structure of two G-quadruplexes in equilibrium in the KRAS promoter." Nucleic Acids Res., 48, 9336-9345. doi: 10.1093/nar/gkaa387.
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 KRAS 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
3 G-tetrads, 1 G4 helix, 1 G4 stem, UUUU, parallel, 4+0, 2(-P-P-P)

Cartoon-block schematics in six views (download the tarball)

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List of 3 G-tetrads

 1 glyco-bond=---- sugar=---. groove=---- planarity=0.677 type=bowl   O+ nts=4 GGGG A.DG2,A.DG6,A.DG11,A.DG25
 2 glyco-bond=---- sugar=..-. groove=---- planarity=0.602 type=other  O+ nts=4 GGGG A.DG3,A.DG7,A.DG12,A.DG26
 3 glyco-bond=-s-- sugar=-..- groove=wn-- planarity=0.507 type=saddle Z- nts=4 GGGG A.DG4,A.DG32,A.DG13,A.DG27

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-tetrads, INTRA-molecular, with 1 stem
 1  glyco-bond=---- sugar=---. groove=---- WC-->Major O+ nts=4 GGGG A.DG2,A.DG6,A.DG11,A.DG25
 2  glyco-bond=---- sugar=..-. groove=---- WC-->Major O+ nts=4 GGGG A.DG3,A.DG7,A.DG12,A.DG26
 3  glyco-bond=-s-- sugar=-..- groove=wn-- WC-->Major Z- nts=4 GGGG A.DG4,A.DG32,A.DG13,A.DG27
  step#1  pm(>>,forward)  area=18.70 rise=3.26 twist=24.5
  step#2  pm(>>,forward)  area=16.65 rise=3.59 twist=27.5
  strand#1 DNA glyco-bond=--- sugar=-.- nts=3 GGG A.DG2,A.DG3,A.DG4
  strand#2 DNA glyco-bond=--s sugar=-.. nts=3 GGG A.DG6,A.DG7,A.DG32
  strand#3 DNA glyco-bond=--- sugar=--. nts=3 GGG A.DG11,A.DG12,A.DG13
  strand#4 DNA glyco-bond=--- sugar=..- nts=3 GGG A.DG25,A.DG26,A.DG27

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2 stacking diagrams 
 1  glyco-bond=---- sugar=---. groove=---- WC-->Major O+ nts=4 GGGG A.DG2,A.DG6,A.DG11,A.DG25
 2  glyco-bond=---- sugar=..-. groove=---- WC-->Major O+ nts=4 GGGG A.DG3,A.DG7,A.DG12,A.DG26
  step#1  pm(>>,forward)  area=18.70 rise=3.26 twist=24.5

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 2  glyco-bond=---- sugar=..-. groove=---- WC-->Major O+ nts=4 GGGG A.DG3,A.DG7,A.DG12,A.DG26
 3  glyco-bond=-s-- sugar=-..- groove=wn-- WC-->Major Z- nts=4 GGGG A.DG4,A.DG32,A.DG13,A.DG27
  step#2  pm(>>,forward)  area=16.65 rise=3.59 twist=27.5

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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, 2 G-tetrads, 3 loops, INTRA-molecular, UUUU, parallel, 4+0, 2(-P-P-P)
 1  glyco-bond=---- sugar=---. groove=---- WC-->Major O+ nts=4 GGGG A.DG2,A.DG6,A.DG11,A.DG25
 2  glyco-bond=---- sugar=..-. groove=---- WC-->Major O+ nts=4 GGGG A.DG3,A.DG7,A.DG12,A.DG26
  step#1  pm(>>,forward)  area=18.70 rise=3.26 twist=24.5
  strand#1  U DNA glyco-bond=-- sugar=-. nts=2 GG A.DG2,A.DG3
  strand#2  U DNA glyco-bond=-- sugar=-. nts=2 GG A.DG6,A.DG7
  strand#3  U DNA glyco-bond=-- sugar=-- nts=2 GG A.DG11,A.DG12
  strand#4  U DNA glyco-bond=-- sugar=.. nts=2 GG A.DG25,A.DG26
  loop#1 type=propeller strands=[#1,#2] nts=2 GC A.DG4,A.DC5
  loop#2 type=propeller strands=[#2,#3] nts=3 TTT A.DT8,A.DT9,A.DT10
  loop#3 type=propeller strands=[#3,#4] nts=12 GAAGAGGGAAGA A.DG13,A.DA14,A.DA15,A.DG16,A.DA17,A.DG18,A.DG19,A.DG20,A.DA21,A.DA22,A.DG23,A.DA24

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List of 1 non-stem G4-loop (including the two closing Gs)

 1 type=diagonal  helix=#1 nts=6 GGGAGG A.DG27,A.DG28,A.DG29,A.DA30,A.DG31,A.DG32