DSSR-derived G-quadruplex features in PDB entry 2ld8
- Structure of human telomeric DNA in crowded solution
- Heddi, B., Phan, A.T.: (2011) "Structure of Human Telomeric DNA in Crowded Solution." J.Am.Chem.Soc.
- G-quadruplex structures formed by DNA at the human telomeres are attractive anticancer targets. Human telomeric sequences can adopt a diverse range of intramolecular G-quadruplex conformations: a parallel-stranded conformation was observed in the crystalline state, while at least four other forms were seen in K(+) solution, raising the question of which conformation is favored in crowded cellular environment. Here, we report the first NMR structure of a human telomeric G-quadruplex in crowded solution. We show that four different G-quadruplex conformations are converted to a propeller-type parallel-stranded G-quadruplex in K(+)-containing crowded solution due to water depletion. This study also reveals the formation of a new higher-order G-quadruplex structure under molecular crowding conditions. Our molecular dynamics simulations of solvent distribution provide insights at molecular level on the formation of parallel-stranded G-quadruplex in environment depleted of water. These results regarding human telomeric DNA can be extended to oncogenic promoters and other genomic G-rich sequences.
- G4 notes
- 3 G-tetrads, 1 G4 helix, 1 G4 stem · 3(-P-P-P), parallel(4+0), UUUU
1 glyco-bond=---- groove=---- planarity=0.331 type=other nts=4 GGGG A.DG3,A.DG9,A.DG15,A.DG21 2 glyco-bond=---- groove=---- planarity=0.442 type=bowl-2 nts=4 GGGG A.DG4,A.DG10,A.DG16,A.DG22 3 glyco-bond=---- groove=---- planarity=0.458 type=bowl nts=4 GGGG A.DG5,A.DG11,A.DG17,A.DG23
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
In DSSR, a G4-stem is defined as a G4-helix with backbone connectivity. Bulges are also allowed along each of the four strands.