DSSR-derived G-quadruplex features in PDB entry 6k3x
Poster "DSSR-Enabled Automatic Identification and Annotation of G-quadruplexes in the PDB" presented at the RNA2020 online meeting
Citation: before a paper dedicated to the DSSR-G4 module comes out, please cite the 2015 DSSR paper published in Nucleic Acids Research.
- G-quadruplex complex with linear dinucleotide d(ag)
- Winnerdy, F.R., Das, P., Heddi, B., Phan, A.T.: (2019) "Solution Structures of a G-Quadruplex Bound to Linear- and Cyclic-Dinucleotides." J.Am.Chem.Soc., 141, 18038-18047.
- Cyclic dinucleotides have emerged as important secondary messengers and cell signaling molecules that regulate several cell responses. A guanine-deficit G-quadruplex structure formation by a sequence containing (4n - 1) guanines, n denoting the number of G-tetrad layers, was previously reported. Here, a (4n - 1) G-quadruplex structure is shown to be capable of binding guanine-containing dinucleotides in micromolar affinity. The guanine base of the dinucleotides interacts with a vacant G-triad, forming four additional Hoogsteen hydrogen bonds to complete a G-tetrad. Solution structures of two complexes, both comprised of a (4n - 1) G-quadruplex structure, one bound to a linear dinucleotide (d(AG)) and the other to a cyclic dinucleotide (cGAMP), are solved using NMR spectroscopy. The latter suggests sufficiently strong interaction between the guanine base of the dinucleotide and the vacant G-triad, which acts as an anchor point of binding. The binding interfaces from the two solution structures provide useful information for specific ligand design. The results also infer that other guanine-containing metabolites of a similar size have the capability of binding G-quadruplexes, potentially affecting the expression of the metabolites and functionality of the bound G-quadruplexes.
- G4 notes
- 3 G-tetrads, 1 G4 helix, 1 G4 stem · 2(-P-P-P), parallel(4+0), UUUU
1 glyco-bond=---- groove=---- planarity=0.079 type=planar nts=4 GGGG A.DG3,A.DG6,A.DG10,A.DG14 2 glyco-bond=---- groove=---- planarity=0.066 type=planar nts=4 GGGG A.DG4,A.DG7,A.DG11,A.DG15 3 glyco-bond=---s groove=--wn planarity=0.071 type=planar nts=4 GGGG A.DG8,A.DG12,A.DG16,B.DG2