DSSR-derived G-quadruplex features in PDB entry 2kyp
- Monomeric human ckit-2 proto-oncogene promoter quadruplex DNA NMR, 12 structures
- Kuryavyi, V., Phan, A.T., Patel, D.J.: (2010) "Solution structures of all parallel-stranded monomeric and dimeric G-quadruplex scaffolds of the human c-kit2 promoter." Nucleic Acids Res., 38, 6757-6773.
- Previous studies have demonstrated that nuclease hypersensitivity regions of several proto-oncogenic DNA promoters, situated upstream of transcription start sites, contain guanine-rich tracts that form intramolecular G-quadruplexes stabilized by stacked G•G•G•G tetrads in monovalent cation solution. The human c-kit oncogenic promoter, an important target in the treatment of gastrointestinal tumors, contains two such stretches of guanine-rich tracts, designated c-kit1 and c-kit2. Our previous nuclear magnetic resonance (NMR)-based studies reported on the novel G-quadruplex scaffold of the c-kit1 promoter in K(+)-containing solution, where we showed for the first time that even an isolated guanine was involved in G-tetrad formation. These NMR-based studies are now extended to the c-kit2 promoter, which adopts two distinct all-parallel-stranded conformations in slow exchange, one of which forms a monomeric G-quadruplex (form-I) in 20 mM K(+)-containing solution and the other a novel dimeric G-quadruplex (form-II) in 100 mM K(+)-containing solution. The c-kit2 promoter dimeric form-II G-quadruplex adopts an unprecedented all-parallel-stranded topology where individual c-kit2 promoter strands span a pair of three-G-tetrad-layer-containing all-parallel-stranded G-quadruplexes aligned in a 3' to 5'-end orientation, with stacking continuity between G-quadruplexes mediated by a sandwiched A•A non-canonical pair. We propose that strand exchange during recombination events within guanine-rich segments, could potentially be mediated by a synapsis intermediate involving an intergenic parallel-stranded dimeric G-quadruplex.
- G4 notes
- 3 G-tetrads, 1 G4 helix, 1 G4 stem · 3(-P-P-P), parallel(4+0), UUUU
1 glyco-bond=---- groove=---- planarity=0.085 type=planar nts=4 GGGG A.DG2,A.DG6,A.DG14,A.DG18 2 glyco-bond=---- groove=---- planarity=0.072 type=planar nts=4 GGGG A.DG3,A.DG7,A.DG15,A.DG19 3 glyco-bond=---- groove=---- planarity=0.129 type=planar nts=4 GGGG A.DG4,A.DG8,A.DG16,A.DG20
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.