DSSR-derived G-quadruplex features in PDB entry 5mvb
- Solution structure of a human G-quadruplex hybrid-2 form in complex with a gold-ligand
- Wirmer-Bartoschek, J., Bendel, L.E., Jonker, H.R.A., Grun, J.T., Papi, F., Bazzicalupi, C., Messori, L., Gratteri, P., Schwalbe, H.: (2017) "Solution NMR Structure of a Ligand/Hybrid-2-G-Quadruplex Complex Reveals Rearrangements that Affect Ligand Binding." Angew. Chem. Int. Ed. Engl., 56, 7102-7106.
- Telomeric G-quadruplexes have recently emerged as drug targets in cancer research. Herein, we present the first NMR structure of a telomeric DNA G-quadruplex that adopts the biologically relevant hybrid-2 conformation in a ligand-bound state. We solved the complex with a metalorganic gold(III) ligand that stabilizes G-quadruplexes. Analysis of the free and bound structures reveals structural changes in the capping region of the G-quadruplex. The ligand is sandwiched between one terminal G-tetrad and a flanking nucleotide. This complex structure involves a major structural rearrangement compared to the free G-quadruplex structure as observed for other G-quadruplexes in different conformations, invalidating simple docking approaches to ligand-G-quadruplex structure determination.
- G4 notes
- 3 G-tetrads, 1 G4 helix, 1 G4 stem · 3(-Lw-Ln-P), hybrid-2(3+1), UDUU
1 glyco-bond=s-ss groove=wn-- planarity=0.348 type=bowl nts=4 GGGG A.DG4,A.DG12,A.DG16,A.DG22 2 glyco-bond=-s-- groove=wn-- planarity=0.211 type=other nts=4 GGGG A.DG5,A.DG11,A.DG17,A.DG23 3 glyco-bond=-s-- groove=wn-- planarity=0.307 type=bowl nts=4 GGGG A.DG6,A.DG10,A.DG18,A.DG24
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.