Summary information and primary citation

PDB-id
5mcr
Class
DNA
Method
NMR
Summary
Quadruplex with flipped tetrad formed by an artificial sequence
Reference
Dickerhoff J, Haase L, Langel W, Weisz K (2017): "Tracing Effects of Fluorine Substitutions on G-Quadruplex Conformational Changes." ACS Chem. Biol., 12, 1308-1315. doi: 10.1021/acschembio.6b01096.
Abstract
A human telomere sequence that folds into an intramolecular (3 + 1)-hybrid G-quadruplex was modified by the incorporation of 2'-fluoro-2'-deoxyriboguanosines (<sub>F</sub>G) into syn positions of its outer tetrad. A circular dichroism and NMR spectral analysis reveals a nearly quantitative switch of the G-tetrad polarity with concerted syn↔anti transitions of all four G residues. These observations follow findings on a <sub>F</sub>G-substituted (3 + 1)-hybrid quadruplex with a different fold, suggesting a more general propensity of hybrid-type quadruplexes to undergo a tetrad polarity reversal. Two out of the three <sub>F</sub>G analogs in both modified quadruplexes adopt an S-type sugar pucker, challenging a sole contribution of N-type sugars in enforcing an anti glycosidic torsion angle associated with the tetrad flip. NMR restrained three-dimensional structures of the two substituted quadruplexes reveal a largely conserved overall fold but significant rearrangements of the overhang and loop nucleotides capping the flipped tetrad. Sugar pucker preferences of the <sub>F</sub>G analogs may be rationalized by different orientations of the fluorine atom and its resistance to be positioned within the narrow groove with its highly negative electrostatic potential and spine of water molecules.
G4 notes
3 G-tetrads, 1 G4 helix, 1 G4 stem, UUUD, hybrid2, 3+1, 3(-PD+Lw)

Cartoon-block schematics in six views (download the tarball)

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List of 3 G-tetrads

 1 glyco-bond=---s sugar=3--. groove=--wn planarity=0.292 type=other  N+ nts=4 gggG A.GF0/1,A.GF2/6,A.GF2/20,A.DG16
 2 glyco-bond=---s sugar=3--- groove=--wn planarity=0.184 type=other  N+ nts=4 GGGG A.DG2,A.DG7,A.DG21,A.DG15
 3 glyco-bond=---s sugar=---- groove=--wn planarity=0.244 type=other  N+ nts=4 GGGG A.DG3,A.DG8,A.DG22,A.DG14

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-tetrads, INTRA-molecular, with 1 stem
 1  glyco-bond=---s sugar=3--. groove=--wn WC-->Major N+ nts=4 gggG A.GF0/1,A.GF2/6,A.GF2/20,A.DG16
 2  glyco-bond=---s sugar=3--- groove=--wn WC-->Major N+ nts=4 GGGG A.DG2,A.DG7,A.DG21,A.DG15
 3  glyco-bond=---s sugar=---- groove=--wn WC-->Major N+ nts=4 GGGG A.DG3,A.DG8,A.DG22,A.DG14
  step#1  pm(>>,forward)  area=13.95 rise=3.45 twist=27.1
  step#2  pm(>>,forward)  area=14.46 rise=3.63 twist=23.2
  strand#1 DNA glyco-bond=--- sugar=33- nts=3 gGG A.GF0/1,A.DG2,A.DG3
  strand#2 DNA glyco-bond=--- sugar=--- nts=3 gGG A.GF2/6,A.DG7,A.DG8
  strand#3 DNA glyco-bond=--- sugar=--- nts=3 gGG A.GF2/20,A.DG21,A.DG22
  strand#4 DNA glyco-bond=sss sugar=.-- nts=3 GGG A.DG16,A.DG15,A.DG14

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2 stacking diagrams 
 1  glyco-bond=---s sugar=3--. groove=--wn WC-->Major N+ nts=4 gggG A.GF0/1,A.GF2/6,A.GF2/20,A.DG16
 2  glyco-bond=---s sugar=3--- groove=--wn WC-->Major N+ nts=4 GGGG A.DG2,A.DG7,A.DG21,A.DG15
  step#1  pm(>>,forward)  area=13.95 rise=3.45 twist=27.1

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 2  glyco-bond=---s sugar=3--- groove=--wn WC-->Major N+ nts=4 GGGG A.DG2,A.DG7,A.DG21,A.DG15
 3  glyco-bond=---s sugar=---- groove=--wn WC-->Major N+ nts=4 GGGG A.DG3,A.DG8,A.DG22,A.DG14
  step#2  pm(>>,forward)  area=14.46 rise=3.63 twist=23.2

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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, 3 G-tetrads, 3 loops, INTRA-molecular, UUUD, hybrid2, 3+1, 3(-PD+Lw)
 1  glyco-bond=---s sugar=3--. groove=--wn WC-->Major N+ nts=4 gggG A.GF0/1,A.GF2/6,A.GF2/20,A.DG16
 2  glyco-bond=---s sugar=3--- groove=--wn WC-->Major N+ nts=4 GGGG A.DG2,A.DG7,A.DG21,A.DG15
 3  glyco-bond=---s sugar=---- groove=--wn WC-->Major N+ nts=4 GGGG A.DG3,A.DG8,A.DG22,A.DG14
  step#1  pm(>>,forward)  area=13.95 rise=3.45 twist=27.1
  step#2  pm(>>,forward)  area=14.46 rise=3.63 twist=23.2
  strand#1  U DNA glyco-bond=--- sugar=33- nts=3 gGG A.GF0/1,A.DG2,A.DG3
  strand#2  U DNA glyco-bond=--- sugar=--- nts=3 gGG A.GF2/6,A.DG7,A.DG8
  strand#3  U DNA glyco-bond=--- sugar=--- nts=3 gGG A.GF2/20,A.DG21,A.DG22
  strand#4  D DNA glyco-bond=sss sugar=.-- nts=3 GGG A.DG16,A.DG15,A.DG14
  loop#1 type=propeller strands=[#1,#2] nts=2 AT A.DA4,A.DT5
  loop#2 type=diagonal  strands=[#2,#4] nts=5 ACACA A.DA9,A.DC10,A.DA11,A.DC12,A.DA13
  loop#3 type=lateral   strands=[#4,#3] nts=3 GAC A.DG17,A.DA18,A.DC19

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