DSSR-derived G-quadruplex features in PDB entry 2a5r
- Complex of tetra-(4-n-methylpyridyl) porphin with monomeric parallel-stranded DNA tetraplex, snap-back 3+1 3' G-tetrad, single-residue chain reversal loops, gag triad in the context of gaag diagonal loop, c-myc promoter, NMR, 6 struct
- Phan, A.T., Kuryavyi, V., Gaw, H.Y., Patel, D.J.: (2005) "Small-molecule interaction with a five-guanine-tract G-quadruplex structure from the human MYC promoter." Nat.Chem.Biol., 1, 167-173.
- It has been widely accepted that DNA can adopt other biologically relevant structures beside the Watson-Crick double helix. One recent important example is the guanine-quadruplex (G-quadruplex) structure formed by guanine tracts found in the MYC (or c-myc) promoter region, which regulates the transcription of the MYC oncogene. Stabilization of this G-quadruplex by ligands, such as the cationic porphyrin TMPyP4, decreases the transcriptional level of MYC. Here, we report the first structure of a DNA fragment containing five guanine tracts from this region. An unusual G-quadruplex fold, which was derived from NMR restraints using unambiguous model-independent resonance assignment approaches, involves a core of three stacked guanine tetrads formed by four parallel guanine tracts with all anti guanines and a snapback 3'-end syn guanine. We have determined the structure of the complex formed between this G-quadruplex and TMPyP4. This structural information, combined with details of small-molecule interaction, provides a platform for the design of anticancer drugs targeting multi-guanine-tract sequences that are found in the MYC and other oncogenic promoters, as well as in telomeres.
- G4 notes
- 3 G-tetrads, 1 G4 helix, 1 G4 stem · 2(-P-P-P), parallel(4+0), UUUU
1 glyco-bond=---- groove=---- planarity=0.114 type=planar nts=4 GGGG A.DG4,A.DG8,A.DG13,A.DG17 2 glyco-bond=---- groove=---- planarity=0.240 type=other nts=4 GGGG A.DG5,A.DG9,A.DG14,A.DG18 3 glyco-bond=-s-- groove=wn-- planarity=0.304 type=other nts=4 GGGG A.DG6,A.DG24,A.DG15,A.DG19
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(-P-P-P), parallel(4+0)
List of 1 non-stem G4-loop (including the two closing Gs)
1 type=diagonal helix=#1 nts=6 GGAAGG A.DG19,A.DG20,A.DA21,A.DA22,A.DG23,A.DG24