Summary information [schematics · tetrads · helices · stems · costacks · homepage]

PDB-id
2hri
Class
DNA
Method
X-ray (2.09 Å)
Summary
A parallel stranded human telomeric quadruplex in complex with the porphyrin tmpyp4
Reference
Parkinson, G.N., Ghosh, R., Neidle, S.: (2007) "Structural basis for binding of porphyrin to human telomeres." Biochemistry, 46, 2390-2397.
Abstract
Maintenance of telomere integrity is a hallmark of human cancer, and the single-stranded 3' ends of telomeric DNA are targets for small-molecule anticancer therapies. We report here the crystal structure of a bimolecular human telomeric quadruplex, of the sequence d(TAGGGTTAGGG), in a complex with the quadruplex-binding ligand 5,10,15,20-tetrakis(N-methyl-4-pyridyl)porphyrin (TMPyP4) to a resolution of 2.09 A. The DNA quadruplex topology is parallel-stranded with external double-chain-reversal propeller loops, consistent with previous structural determinations. The porphyrin molecules bind by stacking onto the TTA nucleotides, either as part of the external loop structure or at the 5' region of the stacked quadruplex. This involves stacked on hydrogen-bonded base pairs, formed from those nucleotides not involved in the formation of G-tetrads, and there are thus no direct ligand interactions with G-tetrads. This is in accord with the relative nonselectivity by TMPyP4 for quadruplex DNAs compared to duplex DNA. Porphyrin binding is achieved by remodeling of loops compared to the ligand-free structures. Implications for the design of quadruplex-binding ligands are discussed, together with a model for the formation of anaphase bridges, which are observed following cellular treatment with TMPyP4.
G4 notes
3 G-tetrads, 1 G4 helix, 1 G4 stem · parallel(4+0), UUUU

Base-block schematics in six views [summary · tetrads · helices · stems · costacks · homepage]

PyMOL session file PDB file View in 3Dmol.js

List of 3 G-tetrads [summary · schematics · helices · stems · costacks · homepage]

 1 glyco-bond=---- groove=---- planarity=0.153 type=planar nts=4 GGGG A.DG3,A.DG9,B.DG14,B.DG20
 2 glyco-bond=---- groove=---- planarity=0.092 type=planar nts=4 GGGG A.DG4,A.DG10,B.DG15,B.DG21
 3 glyco-bond=---- groove=---- planarity=0.065 type=planar nts=4 GGGG A.DG5,A.DG11,B.DG16,B.DG22

List of 1 G4-helix [summary · schematics · tetrads · stems · costacks · homepage]

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=---- groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG9,B.DG14,B.DG20
 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG4,A.DG10,B.DG15,B.DG21
 3  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG5,A.DG11,B.DG16,B.DG22
  step#1  pm(>>,forward)  area=15.09 rise=3.32 twist=25.2
  step#2  pm(>>,forward)  area=12.36 rise=3.31 twist=29.3
  strand#1 DNA glyco-bond=--- nts=3 GGG A.DG3,A.DG4,A.DG5
  strand#2 DNA glyco-bond=--- nts=3 GGG A.DG9,A.DG10,A.DG11
  strand#3 DNA glyco-bond=--- nts=3 GGG B.DG14,B.DG15,B.DG16
  strand#4 DNA glyco-bond=--- nts=3 GGG B.DG20,B.DG21,B.DG22

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2 stacking diagrams
 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG9,B.DG14,B.DG20
2 glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG4,A.DG10,B.DG15,B.DG21
step#1 pm(>>,forward) area=15.09 rise=3.32 twist=25.2

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 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG4,A.DG10,B.DG15,B.DG21
3 glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG5,A.DG11,B.DG16,B.DG22
step#2 pm(>>,forward) area=12.36 rise=3.31 twist=29.3

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List of 1 G4-stem [summary · schematics · tetrads · helices · costacks · homepage]

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-tetrad layers, 2 loops, inter-molecular, UUUU, parallel, parallel(4+0)

 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG9,B.DG14,B.DG20
 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG4,A.DG10,B.DG15,B.DG21
 3  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG5,A.DG11,B.DG16,B.DG22
  step#1  pm(>>,forward)  area=15.09 rise=3.32 twist=25.2
  step#2  pm(>>,forward)  area=12.36 rise=3.31 twist=29.3
  strand#1  U DNA glyco-bond=--- nts=3 GGG A.DG3,A.DG4,A.DG5
  strand#2  U DNA glyco-bond=--- nts=3 GGG A.DG9,A.DG10,A.DG11
  strand#3  U DNA glyco-bond=--- nts=3 GGG B.DG14,B.DG15,B.DG16
  strand#4  U DNA glyco-bond=--- nts=3 GGG B.DG20,B.DG21,B.DG22
  loop#1 type=propeller strands=[#1,#2] nts=3 TTA A.DT6,A.DT7,A.DA8
  loop#2 type=propeller strands=[#3,#4] nts=3 TTA B.DT17,B.DT18,B.DA19

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List of 0 G4 coaxial stacks [summary · schematics · tetrads · helices · stems · homepage]

List of 0 non-stem G4-loops (including the two closing Gs)