DSSR-derived G-quadruplex features in PDB entry 2jt7
- NMR solution structure of the 4:1 distamycin a-[d(tggggt)]4 complex
- Martino, L., Virno, A., Pagano, B., Virgilio, A., Di Micco, S., Galeone, A., Giancola, C., Bifulco, G., Mayol, L., Randazzo, A.: (2007) "Structural and thermodynamic studies of the interaction of distamycin A with the parallel quadruplex structure [d(TGGGGT)]4." J.Am.Chem.Soc., 129, 16048-16056.
- The complex between distamycin A and the parallel DNA quadruplex [d(TGGGGT)]4 has been studied by 1H NMR spectroscopy and isothermal titration calorimetry (ITC). To unambiguously assert that distamycin A interacts with the grooves of the quadruplex [d(TGGGGT)]4, we have analyzed the NMR titration profile of a modified quadruplex, namely [d(TGGMeGGT)]4, and we have applied the recently developed differential frequency-saturation transfer difference (DF-STD) method, for assessing the ligand-DNA binding mode. The three-dimensional structure of the 4:1 distamycin A/[d(TGGGGT)]4 complex has been determined by an in-depth NMR study followed by dynamics and mechanics calculations. All results unequivocally indicate that distamycin molecules interact with [d(TGGGGT)]4 in a 4:1 binding mode, with two antiparallel distamycin dimers that bind simultaneously two opposite grooves of the quadruplex. The affinity between distamycin A and [d(TGGGGT)]4 enhances ( approximately 10-fold) when the ratio of distamycin A to the quadruplex is increased. In this paper we report the first three-dimensional structure of a groove-binder molecule complexed to a DNA quadruplex structure.
- G4 notes
- 4 G-tetrads, 1 G4 helix, 1 G4 stem · parallel(4+0), UUUU
1 glyco-bond=---- groove=---- planarity=0.223 type=other nts=4 GGGG A.DG2,F.DG2,B.DG2,E.DG2 2 glyco-bond=---- groove=---- planarity=0.430 type=other nts=4 GGGG A.DG3,F.DG3,B.DG3,E.DG3 3 glyco-bond=---- groove=---- planarity=0.313 type=saddle nts=4 GGGG A.DG4,F.DG4,B.DG4,E.DG4 4 glyco-bond=---- groove=---- planarity=0.253 type=bowl-2 nts=4 GGGG A.DG5,F.DG5,B.DG5,E.DG5
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.