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PDB-id
2e4i
Class
DNA
Method
NMR
Summary
Human telomeric DNA mixed-parallel-antiparallel quadruplex under physiological ionic conditions stabilized by proper incorporation of 8-bromoguanosines
Reference
Matsugami, A., Xu, Y., Noguchi, Y., Sugiyama, H., Katahira, M.: (2007) "Structure of a human telomeric DNA sequence stabilized by 8-bromoguanosine substitutions, as determined by NMR in a K+ solution." Febs J., 274, 3545-3556.
Abstract
The structure of human telomeric DNA is controversial; it depends upon the sequence contexts and the methodologies used to determine it. The solution structure in the presence of K(+) is particularly interesting, but the structure is yet to be elucidated, due to possible conformational heterogeneity. Here, a unique strategy is applied to stabilize one such structure in a K(+) solution by substituting guanosines with 8-bromoguanosines at proper positions. The resulting spectra are cleaner and led to determination of the structure at a high atomic resolution. This demonstrates that the application of 8-bromoguanosine is a powerful tool to overcome the difficulty of nucleic acid structure determination arising from conformational heterogeneity. The obtained structure is a mixed-parallel/antiparallel quadruplex. The structure of telomeric DNA was recently reported in another study, in which stabilization was brought about by mutation and resultant additional interactions [Luu KN, Phan AT, Kuryavyi V, Lacroix L & Patel DJ (2006) Structure of the human telomere in K(+) solution: an intramolecular (3+1) G-quadruplex scaffold. J Am Chem Soc 128, 9963-9970]. The structure of the guanine tracts was similar between the two. However, a difference was seen for loops connecting guanine tracts, which may play a role in the higher order arrangement of telomeres. Our structure can be utilized to design a small molecule which stabilizes the quadruplex. This type of molecule is supposed to inhibit a telomerase and thus is expected to be a candidate anticancer drug.
G4 notes
3 G-tetrads, 1 G4 helix, 1 G4 stem · 3(-P-Lw-Ln), hybrid-1(3+1), UUDU

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=ss-s groove=-wn- planarity=0.238 type=other  nts=4 ggGg A.BGM2,A.BGM8,A.DG16,A.BGM20
 2 glyco-bond=--s- groove=-wn- planarity=0.336 type=other  nts=4 GGgG A.DG3,A.DG9,A.BGM15,A.DG21
 3 glyco-bond=--s- groove=-wn- planarity=0.459 type=bowl   nts=4 GGgG A.DG4,A.DG10,A.BGM14,A.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, INTRA-molecular, with 1 stem

 1  glyco-bond=ss-s groove=-wn- Major-->WC nts=4 ggGg A.BGM2,A.BGM8,A.DG16,A.BGM20
 2  glyco-bond=--s- groove=-wn- WC-->Major nts=4 GGgG A.DG3,A.DG9,A.BGM15,A.DG21
 3  glyco-bond=--s- groove=-wn- WC-->Major nts=4 GGgG A.DG4,A.DG10,A.BGM14,A.DG22
  step#1  mm(<>,outward)  area=18.49 rise=3.73 twist=14.0
  step#2  pm(>>,forward)  area=12.94 rise=3.75 twist=24.2
  strand#1 DNA glyco-bond=s-- nts=3 gGG A.BGM2,A.DG3,A.DG4
  strand#2 DNA glyco-bond=s-- nts=3 gGG A.BGM8,A.DG9,A.DG10
  strand#3 DNA glyco-bond=-ss nts=3 Ggg A.DG16,A.BGM15,A.BGM14
  strand#4 DNA glyco-bond=s-- nts=3 gGG A.BGM20,A.DG21,A.DG22

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2 stacking diagrams
 1  glyco-bond=ss-s groove=-wn- Major-->WC nts=4 ggGg A.BGM2,A.BGM8,A.DG16,A.BGM20
2 glyco-bond=--s- groove=-wn- WC-->Major nts=4 GGgG A.DG3,A.DG9,A.BGM15,A.DG21
step#1 mm(<>,outward) area=18.49 rise=3.73 twist=14.0

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 2  glyco-bond=--s- groove=-wn- WC-->Major nts=4 GGgG A.DG3,A.DG9,A.BGM15,A.DG21
3 glyco-bond=--s- groove=-wn- WC-->Major nts=4 GGgG A.DG4,A.DG10,A.BGM14,A.DG22
step#2 pm(>>,forward) area=12.94 rise=3.75 twist=24.2

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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, 3 loops, INTRA-molecular, UUDU, anti-parallel, 3(-P-Lw-Ln), hybrid-1(3+1)

 1  glyco-bond=ss-s groove=-wn- Major-->WC nts=4 ggGg A.BGM2,A.BGM8,A.DG16,A.BGM20
 2  glyco-bond=--s- groove=-wn- WC-->Major nts=4 GGgG A.DG3,A.DG9,A.BGM15,A.DG21
 3  glyco-bond=--s- groove=-wn- WC-->Major nts=4 GGgG A.DG4,A.DG10,A.BGM14,A.DG22
  step#1  mm(<>,outward)  area=18.49 rise=3.73 twist=14.0
  step#2  pm(>>,forward)  area=12.94 rise=3.75 twist=24.2
  strand#1  U DNA glyco-bond=s-- nts=3 gGG A.BGM2,A.DG3,A.DG4
  strand#2  U DNA glyco-bond=s-- nts=3 gGG A.BGM8,A.DG9,A.DG10
  strand#3  D DNA glyco-bond=-ss nts=3 Ggg A.DG16,A.BGM15,A.BGM14
  strand#4  U DNA glyco-bond=s-- nts=3 gGG A.BGM20,A.DG21,A.DG22
  loop#1 type=propeller strands=[#1,#2] nts=3 TTA A.DT5,A.DT6,A.DA7
  loop#2 type=lateral   strands=[#2,#3] nts=3 TTA A.DT11,A.DT12,A.DA13
  loop#3 type=lateral   strands=[#3,#4] nts=3 TTA A.DT17,A.DT18,A.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)