6K3Y

G-quadruplex complex with cyclic dinucleotide 3'-3' cGAMP

Summary for 6K3Y

• Entry DOI: 10.2210/pdb6k3y/pdb
• Descriptor: DNA (5'-D(*TP*TP*GP*GP*TP*GP*GP*GP*TP*GP*GP*GP*TP*GP*GP*GP*T)-3'), 2-amino-9-[(2R,3R,3aS,5R,7aR,9R,10R,10aS,12R,14aR)-9-(6-amino-9H-purin-9-yl)-3,5,10,12-tetrahydroxy-5,12-dioxidooctahydro-2H,7H-difuro[3,2-d:3',2'-j][1,3,7,9,2,8]tetraoxadiphosphacyclododecin-2-yl]-1,9-dihydro-6H-purin-6-one (2 entities in total)
• Functional Keywords: g-quadruplex, cgamp, dinucleotide, vacancy, dna
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 6075.87

Authors

Winnerdy, F.R.,Heddi, B.,Phan, A.T. (deposition date: 2019-05-22, release date: 2020-01-15, Last modification date: 2024-05-15)

Primary citation

Winnerdy, F.R.,Das, P.,Heddi, B.,Phan, A.T.
Solution Structures of a G-Quadruplex Bound to Linear- and Cyclic-Dinucleotides.
J.Am.Chem.Soc., 141:18038-18047, 2019

PubMed Abstract: 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 (4 - 1) guanines, denoting the number of G-tetrad layers, was previously reported. Here, a (4 - 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 (4 - 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.

PubMed: 31661272
DOI: 10.1021/jacs.9b05642

Experimental method

SOLUTION NMR