DSSR-derived G-quadruplex features in PDB entry 2o3m
Citation: before a paper dedicated to the DSSR-G4 module comes out, please cite the 2015 DSSR paper published in Nucleic Acids Research.
- Monomeric g-DNA tetraplex from human c-kit promoter
- Phan, A.T., Kuryavyi, V.V., Burge, S., Neidle, S., Patel, D.J.: (2007) "Structure of an unprecedented G-quadruplex scaffold in the human c-kit promoter." J.Am.Chem.Soc., 129, 4386-4392.
- The c-kit oncogene is an important target in the treatment of gastrointestinal tumors. A potential approach to inhibition of the expression of this gene involves selective stabilization of G-quadruplex structures that may be induced to form in the c-kit promoter region. Here we report on the structure of an unprecedented intramolecular G-quadruplex formed by a G-rich sequence in the c-kit promoter in K+ solution. The structure represents a new folding topology with several unique features. Most strikingly, an isolated guanine is involved in G-tetrad core formation, despite the presence of four three-guanine tracts. There are four loops: two single-residue double-chain-reversal loops, a two-residue loop, and a five-residue stem-loop, which contain base-pairing alignments. This unique structural scaffold provides a highly specific platform for the future design of ligands specifically targeted to the promoter DNA of c-kit.
- G4 notes
- 3 G-tetrads, 1 G4 helix, 1 G4 stem · 2(-PX+P), parallel(4+0), UUUU
1 glyco-bond=---- groove=---- planarity=0.084 type=planar nts=4 GGGG A.DG2,A.DG6,A.DG10,A.DG13 2 glyco-bond=---- groove=---- planarity=0.112 type=planar nts=4 GGGG A.DG3,A.DG7,A.DG21,A.DG14 3 glyco-bond=---- groove=---- planarity=0.084 type=planar nts=4 GGGG A.DG4,A.DG8,A.DG22,A.DG15
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.
Stem#1, 2 G-tetrad layers, 3 loops, INTRA-molecular, UUUU, parallel, 2(-PX+P), parallel(4+0)
List of 2 non-stem G4-loops (including the two closing Gs)
1* type=V-shaped helix=#1 nts=5 GGGCG A.DG6,A.DG7,A.DG8,A.DC9,A.DG10 2 type=lateral helix=#1 nts=4 GCTG A.DG10,A.DC11,A.DT12,A.DG13