Summary information

PDB id
6k3x
Class
DNA
Method
NMR
Summary
G-quadruplex complex with linear dinucleotide d(ag)
Reference
Winnerdy FR, Das P, Heddi B, Phan AT (2019): "Solution Structures of a G-Quadruplex Bound to Linear- and Cyclic-Dinucleotides." J.Am.Chem.Soc., 141, 18038-18047. doi: 10.1021/jacs.9b05642.
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 (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

Base-block schematics in six views

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List of 3 G-tetrads

 1 glyco-bond=---- sugar=--.- groove=---- planarity=0.079 type=planar nts=4 GGGG A.DG3,A.DG6,A.DG10,A.DG14
 2 glyco-bond=---- sugar=-.-- groove=---- planarity=0.066 type=planar nts=4 GGGG A.DG4,A.DG7,A.DG11,A.DG15
 3 glyco-bond=---s sugar=---- groove=--wn planarity=0.071 type=planar nts=4 GGGG A.DG8,A.DG12,A.DG16,B.DG2

List of 1 G4-helix

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, inter-molecular, with 1 stem

 1  glyco-bond=---- sugar=--.- groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG6,A.DG10,A.DG14
 2  glyco-bond=---- sugar=-.-- groove=---- WC-->Major nts=4 GGGG A.DG4,A.DG7,A.DG11,A.DG15
 3  glyco-bond=s--- sugar=---- groove=n--w WC-->Major nts=4 GGGG B.DG2,A.DG8,A.DG12,A.DG16
  step#1  pm(>>,forward)  area=10.09 rise=3.18 twist=30.4
  step#2  pm(>>,forward)  area=11.83 rise=3.71 twist=30.0
  strand#1 DNA glyco-bond=--s sugar=--- nts=3 GGG A.DG3,A.DG4,B.DG2
  strand#2 DNA glyco-bond=--- sugar=-.- nts=3 GGG A.DG6,A.DG7,A.DG8
  strand#3 DNA glyco-bond=--- sugar=.-- nts=3 GGG A.DG10,A.DG11,A.DG12
  strand#4 DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG14,A.DG15,A.DG16

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2 stacking diagrams 
 1  glyco-bond=---- sugar=--.- groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG6,A.DG10,A.DG14
 2  glyco-bond=---- sugar=-.-- groove=---- WC-->Major nts=4 GGGG A.DG4,A.DG7,A.DG11,A.DG15
  step#1  pm(>>,forward)  area=10.09 rise=3.18 twist=30.4

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 2  glyco-bond=---- sugar=-.-- groove=---- WC-->Major nts=4 GGGG A.DG4,A.DG7,A.DG11,A.DG15
 3  glyco-bond=s--- sugar=---- groove=n--w WC-->Major nts=4 GGGG B.DG2,A.DG8,A.DG12,A.DG16
  step#2  pm(>>,forward)  area=11.83 rise=3.71 twist=30.0

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List of 1 G4-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)

 1  glyco-bond=---- sugar=--.- groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG6,A.DG10,A.DG14
 2  glyco-bond=---- sugar=-.-- groove=---- WC-->Major nts=4 GGGG A.DG4,A.DG7,A.DG11,A.DG15
  step#1  pm(>>,forward)  area=10.09 rise=3.18 twist=30.4
  strand#1  U DNA glyco-bond=-- sugar=-- nts=2 GG A.DG3,A.DG4
  strand#2  U DNA glyco-bond=-- sugar=-. nts=2 GG A.DG6,A.DG7
  strand#3  U DNA glyco-bond=-- sugar=.- nts=2 GG A.DG10,A.DG11
  strand#4  U DNA glyco-bond=-- sugar=-- nts=2 GG A.DG14,A.DG15
  loop#1 type=propeller strands=[#1,#2] nts=1 T A.DT5
  loop#2 type=propeller strands=[#2,#3] nts=2 GT A.DG8,A.DT9
  loop#3 type=propeller strands=[#3,#4] nts=2 GT A.DG12,A.DT13

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