DSSR-derived G-quadruplex features in PDB entry 1l1h
- X-ray (1.75 Å)
- Crystal structure of the quadruplex DNA-drug complex
- Haider, S.M., Parkinson, G.N., Neidle, S.: (2003) "Structure of a G-quadruplex-Ligand Complex." J.Mol.Biol., 326, 117-125.
- Stabilisation of G-quadruplex structures formed from telomeric DNA, by means of quadruplex-selective ligands, is a means of inhibiting the telomerase enzyme from catalysing the synthesis of telomeric DNA repeats. In order to understand the molecular basis of ligand-quadruplex recognition, the crystal structure has been determined of such a complex, at 1.75A resolution. This complex is between a dimeric antiparallel G-quadruplex formed from the Oxytricha nova telomeric DNA sequence d(GGGGTTTTGGGG), and a di-substituted aminoalkylamido acridine compound. The structure shows that the acridine moiety is bound at one end of the stack of G-quartets, within one of the thymine loops. It is held in place by a combination of stacking interactions and specific hydrogen bonds with thymine bases. The stability of the ligand in this binding site has been confirmed by a 2ns molecular dynamics simulation.
- G4 notes
- 4 G-tetrads, 1 G4 helix, 1 G4 stem · (2+2), UDDU
1 glyco-bond=s--s groove=w-n- planarity=0.279 type=bowl nts=4 GGGG A.DG1001,B.DG2004,A.DG1012,B.DG2009 2 glyco-bond=-ss- groove=w-n- planarity=0.192 type=other nts=4 GGGG A.DG1002,B.DG2003,A.DG1011,B.DG2010 3 glyco-bond=s--s groove=w-n- planarity=0.171 type=other nts=4 GGGG A.DG1003,B.DG2002,A.DG1010,B.DG2011 4 glyco-bond=-ss- groove=w-n- planarity=0.202 type=other nts=4 GGGG A.DG1004,B.DG2001,A.DG1009,B.DG2012
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, 4 G-tetrad layers, inter-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.