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

PDB-id
5dww
Class
DNA
Method
X-ray (2.79 Å)
Summary
Structural insights into the quadruplex-duplex 3' interface formed from a telomeric repeat - ttloop
Reference
Russo Krauss, I., Ramaswamy, S., Neidle, S., Haider, S., Parkinson, G.N.: (2016) "Structural Insights into the Quadruplex-Duplex 3' Interface Formed from a Telomeric Repeat: A Potential Molecular Target." J.Am.Chem.Soc., 138, 1226-1233.
Abstract
We report here on an X-ray crystallographic and molecular modeling investigation into the complex 3' interface formed between putative parallel stranded G-quadruplexes and a duplex DNA sequence constructed from the human telomeric repeat sequence TTAGGG. Our crystallographic approach provides a detailed snapshot of a telomeric 3' quadruplex-duplex junction: a junction that appears to have the potential to form a unique molecular target for small molecule binding and interference with telomere-related functions. This unique target is particularly relevant as current high-affinity compounds that bind putative G-quadruplex forming sequences only rarely have a high degree of selectivity for a particular quadruplex. Here DNA junctions were assembled using different putative quadruplex-forming scaffolds linked at the 3' end to a telomeric duplex sequence and annealed to a complementary strand. We successfully generated a series of G-quadruplex-duplex containing crystals, both alone and in the presence of ligands. The structures demonstrate the formation of a parallel folded G-quadruplex and a B-form duplex DNA stacked coaxially. Most strikingly, structural data reveals the consistent formation of a TAT triad platform between the two motifs. This triad allows for a continuous stack of bases to link the quadruplex motif with the duplex region. For these crystal structures formed in the absence of ligands, the TAT triad interface occludes ligand binding at the 3' quadruplex-duplex interface, in agreement with in silico docking predictions. However, with the rearrangement of a single nucleotide, a stable pocket can be produced, thus providing an opportunity for the binding of selective molecules at the interface.
G4 notes
12 G-tetrads, 2 G4 helices, 4 G4 stems, 2 G4 coaxial stacks · 3(-P-P-P), parallel(4+0), UUUU · coaxial interfaces: 5'/5'

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

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List of 12 G-tetrads [summary · schematics · helices · stems · costacks · homepage]

 1 glyco-bond=---- groove=---- planarity=0.138 type=planar nts=4 GGGG A.DG1,A.DG5,A.DG9,A.DG14
 2 glyco-bond=---- groove=---- planarity=0.120 type=planar nts=4 GGGG A.DG2,A.DG6,A.DG10,A.DG15
 3 glyco-bond=---- groove=---- planarity=0.268 type=bowl   nts=4 GGGG A.DG3,A.DG7,A.DG11,A.DG16
 4 glyco-bond=---- groove=---- planarity=0.130 type=planar nts=4 GGGG C.DG1,C.DG5,C.DG9,C.DG14
 5 glyco-bond=---- groove=---- planarity=0.156 type=planar nts=4 GGGG C.DG2,C.DG6,C.DG10,C.DG15
 6 glyco-bond=---- groove=---- planarity=0.306 type=bowl   nts=4 GGGG C.DG3,C.DG7,C.DG11,C.DG16
 7 glyco-bond=---- groove=---- planarity=0.179 type=other  nts=4 GGGG E.DG1,E.DG5,E.DG9,E.DG14
 8 glyco-bond=---- groove=---- planarity=0.246 type=other  nts=4 GGGG E.DG2,E.DG6,E.DG10,E.DG15
 9 glyco-bond=---- groove=---- planarity=0.227 type=other  nts=4 GGGG E.DG3,E.DG7,E.DG11,E.DG16
10 glyco-bond=---- groove=---- planarity=0.204 type=other  nts=4 GGGG G.DG1,G.DG5,G.DG9,G.DG14
11 glyco-bond=---- groove=---- planarity=0.249 type=other  nts=4 GGGG G.DG2,G.DG6,G.DG10,G.DG15
12 glyco-bond=---- groove=---- planarity=0.292 type=bowl   nts=4 GGGG G.DG3,G.DG7,G.DG11,G.DG16

List of 2 G4-helices [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, 6 G-tetrad layers, inter-molecular, with 2 stems

 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG7,A.DG11,A.DG16
 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG2,A.DG6,A.DG10,A.DG15
 3* glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG1,A.DG5,A.DG9,A.DG14
 4  glyco-bond=---- groove=---- Major-->WC nts=4 GGGG C.DG1,C.DG14,C.DG9,C.DG5
 5  glyco-bond=---- groove=---- Major-->WC nts=4 GGGG C.DG2,C.DG15,C.DG10,C.DG6
 6  glyco-bond=---- groove=---- Major-->WC nts=4 GGGG C.DG3,C.DG16,C.DG11,C.DG7
  step#1  mp(<<,backward) area=10.64 rise=3.33 twist=29.0
  step#2  mp(<<,backward) area=11.63 rise=3.41 twist=30.1
  step#3  mm(<>,outward)  area=28.36 rise=3.40 twist=-9.8
  step#4  pm(>>,forward)  area=11.60 rise=3.42 twist=29.6
  step#5  pm(>>,forward)  area=10.35 rise=3.36 twist=28.9
  strand#1 DNA glyco-bond=------ nts=6 GGGGGG A.DG3,A.DG2,A.DG1,C.DG1,C.DG2,C.DG3
  strand#2 DNA glyco-bond=------ nts=6 GGGGGG A.DG7,A.DG6,A.DG5,C.DG14,C.DG15,C.DG16
  strand#3 DNA glyco-bond=------ nts=6 GGGGGG A.DG11,A.DG10,A.DG9,C.DG9,C.DG10,C.DG11
  strand#4 DNA glyco-bond=------ nts=6 GGGGGG A.DG16,A.DG15,A.DG14,C.DG5,C.DG6,C.DG7

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5 stacking diagrams
 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG7,A.DG11,A.DG16
2 glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG2,A.DG6,A.DG10,A.DG15
step#1 mp(<<,backward) area=10.64 rise=3.33 twist=29.0

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 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG2,A.DG6,A.DG10,A.DG15
3* glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG1,A.DG5,A.DG9,A.DG14
step#2 mp(<<,backward) area=11.63 rise=3.41 twist=30.1

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 3* glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG1,A.DG5,A.DG9,A.DG14
4 glyco-bond=---- groove=---- Major-->WC nts=4 GGGG C.DG1,C.DG14,C.DG9,C.DG5
step#3 mm(<>,outward) area=28.36 rise=3.40 twist=-9.8

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 4  glyco-bond=---- groove=---- Major-->WC nts=4 GGGG C.DG1,C.DG14,C.DG9,C.DG5
5 glyco-bond=---- groove=---- Major-->WC nts=4 GGGG C.DG2,C.DG15,C.DG10,C.DG6
step#4 pm(>>,forward) area=11.60 rise=3.42 twist=29.6

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 5  glyco-bond=---- groove=---- Major-->WC nts=4 GGGG C.DG2,C.DG15,C.DG10,C.DG6
6 glyco-bond=---- groove=---- Major-->WC nts=4 GGGG C.DG3,C.DG16,C.DG11,C.DG7
step#5 pm(>>,forward) area=10.35 rise=3.36 twist=28.9

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Helix#2, 6 G-tetrad layers, inter-molecular, with 2 stems

 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG E.DG3,E.DG7,E.DG11,E.DG16
 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG E.DG2,E.DG6,E.DG10,E.DG15
 3* glyco-bond=---- groove=---- WC-->Major nts=4 GGGG E.DG1,E.DG5,E.DG9,E.DG14
 4  glyco-bond=---- groove=---- Major-->WC nts=4 GGGG G.DG1,G.DG14,G.DG9,G.DG5
 5  glyco-bond=---- groove=---- Major-->WC nts=4 GGGG G.DG2,G.DG15,G.DG10,G.DG6
 6  glyco-bond=---- groove=---- Major-->WC nts=4 GGGG G.DG3,G.DG16,G.DG11,G.DG7
  step#1  mp(<<,backward) area=11.03 rise=3.42 twist=29.2
  step#2  mp(<<,backward) area=11.99 rise=3.31 twist=30.2
  step#3  mm(<>,outward)  area=27.27 rise=3.36 twist=-8.9
  step#4  pm(>>,forward)  area=10.41 rise=3.46 twist=30.0
  step#5  pm(>>,forward)  area=10.96 rise=3.40 twist=28.8
  strand#1 DNA glyco-bond=------ nts=6 GGGGGG E.DG3,E.DG2,E.DG1,G.DG1,G.DG2,G.DG3
  strand#2 DNA glyco-bond=------ nts=6 GGGGGG E.DG7,E.DG6,E.DG5,G.DG14,G.DG15,G.DG16
  strand#3 DNA glyco-bond=------ nts=6 GGGGGG E.DG11,E.DG10,E.DG9,G.DG9,G.DG10,G.DG11
  strand#4 DNA glyco-bond=------ nts=6 GGGGGG E.DG16,E.DG15,E.DG14,G.DG5,G.DG6,G.DG7

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5 stacking diagrams
 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG E.DG3,E.DG7,E.DG11,E.DG16
2 glyco-bond=---- groove=---- WC-->Major nts=4 GGGG E.DG2,E.DG6,E.DG10,E.DG15
step#1 mp(<<,backward) area=11.03 rise=3.42 twist=29.2

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 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG E.DG2,E.DG6,E.DG10,E.DG15
3* glyco-bond=---- groove=---- WC-->Major nts=4 GGGG E.DG1,E.DG5,E.DG9,E.DG14
step#2 mp(<<,backward) area=11.99 rise=3.31 twist=30.2

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 3* glyco-bond=---- groove=---- WC-->Major nts=4 GGGG E.DG1,E.DG5,E.DG9,E.DG14
4 glyco-bond=---- groove=---- Major-->WC nts=4 GGGG G.DG1,G.DG14,G.DG9,G.DG5
step#3 mm(<>,outward) area=27.27 rise=3.36 twist=-8.9

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 4  glyco-bond=---- groove=---- Major-->WC nts=4 GGGG G.DG1,G.DG14,G.DG9,G.DG5
5 glyco-bond=---- groove=---- Major-->WC nts=4 GGGG G.DG2,G.DG15,G.DG10,G.DG6
step#4 pm(>>,forward) area=10.41 rise=3.46 twist=30.0

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 5  glyco-bond=---- groove=---- Major-->WC nts=4 GGGG G.DG2,G.DG15,G.DG10,G.DG6
6 glyco-bond=---- groove=---- Major-->WC nts=4 GGGG G.DG3,G.DG16,G.DG11,G.DG7
step#5 pm(>>,forward) area=10.96 rise=3.40 twist=28.8

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List of 4 G4-stems [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, 3 loops, INTRA-molecular, UUUU, parallel, 3(-P-P-P), parallel(4+0)

 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG1,A.DG5,A.DG9,A.DG14
 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG2,A.DG6,A.DG10,A.DG15
 3  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG7,A.DG11,A.DG16
  step#1  pm(>>,forward)  area=11.63 rise=3.41 twist=30.1
  step#2  pm(>>,forward)  area=10.64 rise=3.33 twist=29.0
  strand#1  U DNA glyco-bond=--- nts=3 GGG A.DG1,A.DG2,A.DG3
  strand#2  U DNA glyco-bond=--- nts=3 GGG A.DG5,A.DG6,A.DG7
  strand#3  U DNA glyco-bond=--- nts=3 GGG A.DG9,A.DG10,A.DG11
  strand#4  U DNA glyco-bond=--- nts=3 GGG A.DG14,A.DG15,A.DG16
  loop#1 type=propeller strands=[#1,#2] nts=1 T A.DT4
  loop#2 type=propeller strands=[#2,#3] nts=1 T A.DT8
  loop#3 type=propeller strands=[#3,#4] nts=2 TT A.DT12,A.DT13

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Stem#2, 3 G-tetrad layers, 3 loops, INTRA-molecular, UUUU, parallel, 3(-P-P-P), parallel(4+0)

 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG C.DG1,C.DG5,C.DG9,C.DG14
 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG C.DG2,C.DG6,C.DG10,C.DG15
 3  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG C.DG3,C.DG7,C.DG11,C.DG16
  step#1  pm(>>,forward)  area=11.60 rise=3.42 twist=29.6
  step#2  pm(>>,forward)  area=10.35 rise=3.36 twist=28.9
  strand#1  U DNA glyco-bond=--- nts=3 GGG C.DG1,C.DG2,C.DG3
  strand#2  U DNA glyco-bond=--- nts=3 GGG C.DG5,C.DG6,C.DG7
  strand#3  U DNA glyco-bond=--- nts=3 GGG C.DG9,C.DG10,C.DG11
  strand#4  U DNA glyco-bond=--- nts=3 GGG C.DG14,C.DG15,C.DG16
  loop#1 type=propeller strands=[#1,#2] nts=1 T C.DT4
  loop#2 type=propeller strands=[#2,#3] nts=1 T C.DT8
  loop#3 type=propeller strands=[#3,#4] nts=2 TT C.DT12,C.DT13

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Stem#3, 3 G-tetrad layers, 3 loops, INTRA-molecular, UUUU, parallel, 3(-P-P-P), parallel(4+0)

 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG E.DG1,E.DG5,E.DG9,E.DG14
 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG E.DG2,E.DG6,E.DG10,E.DG15
 3  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG E.DG3,E.DG7,E.DG11,E.DG16
  step#1  pm(>>,forward)  area=11.99 rise=3.31 twist=30.2
  step#2  pm(>>,forward)  area=11.03 rise=3.42 twist=29.2
  strand#1  U DNA glyco-bond=--- nts=3 GGG E.DG1,E.DG2,E.DG3
  strand#2  U DNA glyco-bond=--- nts=3 GGG E.DG5,E.DG6,E.DG7
  strand#3  U DNA glyco-bond=--- nts=3 GGG E.DG9,E.DG10,E.DG11
  strand#4  U DNA glyco-bond=--- nts=3 GGG E.DG14,E.DG15,E.DG16
  loop#1 type=propeller strands=[#1,#2] nts=1 T E.DT4
  loop#2 type=propeller strands=[#2,#3] nts=1 T E.DT8
  loop#3 type=propeller strands=[#3,#4] nts=2 TT E.DT12,E.DT13

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Stem#4, 3 G-tetrad layers, 3 loops, INTRA-molecular, UUUU, parallel, 3(-P-P-P), parallel(4+0)

 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG G.DG1,G.DG5,G.DG9,G.DG14
 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG G.DG2,G.DG6,G.DG10,G.DG15
 3  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG G.DG3,G.DG7,G.DG11,G.DG16
  step#1  pm(>>,forward)  area=10.41 rise=3.46 twist=30.0
  step#2  pm(>>,forward)  area=10.96 rise=3.40 twist=28.8
  strand#1  U DNA glyco-bond=--- nts=3 GGG G.DG1,G.DG2,G.DG3
  strand#2  U DNA glyco-bond=--- nts=3 GGG G.DG5,G.DG6,G.DG7
  strand#3  U DNA glyco-bond=--- nts=3 GGG G.DG9,G.DG10,G.DG11
  strand#4  U DNA glyco-bond=--- nts=3 GGG G.DG14,G.DG15,G.DG16
  loop#1 type=propeller strands=[#1,#2] nts=1 T G.DT4
  loop#2 type=propeller strands=[#2,#3] nts=1 T G.DT8
  loop#3 type=propeller strands=[#3,#4] nts=2 TT G.DT12,G.DT13

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List of 2 G4 coaxial stacks [summary · schematics · tetrads · helices · stems · homepage]

 1 G4 helix#1 contains 2 G4 stems: [#1,#2]  [5'/5']
 2 G4 helix#2 contains 2 G4 stems: [#3,#4]  [5'/5']

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