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

PDB-id
2jpz
Class
DNA
Method
NMR
Summary
Human telomere DNA quadruplex structure in k+ solution hybrid-2 form
Reference
Dai, J., Carver, M., Punchihewa, C., Jones, R.A., Yang, D.: (2007) "Structure of the Hybrid-2 type intramolecular human telomeric G-quadruplex in K+ solution: insights into structure polymorphism of the human telomeric sequence." Nucleic Acids Res., 35, 4927-4940.
Abstract
Formation of the G-quadruplex in the human telomeric sequence can inhibit the activity of telomerase, thus the intramolecular telomeric G-quadruplexes have been considered as an attractive anticancer target. Information of intramolecular telomeric G-quadruplex structures formed under physiological conditions is important for structure-based drug design. Here, we report the first structure of the major intramolecular G-quadruplex formed in a native, non-modified human telomeric sequence in K(+) solution. This is a hybrid-type mixed parallel/antiparallel-G-stranded G-quadruplex, one end of which is covered by a novel T:A:T triple capping structure. This structure (Hybrid-2) and the previously reported Hybrid-1 structure differ in their loop arrangements, strand orientations and capping structures. The distinct capping structures appear to be crucial for the favored formation of the specific hybrid-type intramolecular telomeric G-quadruplexes, and may provide specific binding sites for drug targeting. Our study also shows that while the hybrid-type G-quadruplexes appear to be the major conformations in K(+) solution, human telomeric sequences are always in equilibrium between Hybrid-1 and Hybrid-2 structures, which is largely determined by the 3'-flanking sequence. Furthermore, both hybrid-type G-quadruplexes suggest a straightforward means for multimer formation with effective packing in the human telomeric sequence and provide important implications for drug targeting of G-quadruplexes in human telomeres.
G4 notes
3 G-tetrads, 1 G4 helix, 1 G4 stem · 3(-Lw-Ln-P), hybrid-2(3+1), UDUU

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=s-ss groove=wn-- planarity=0.189 type=other  nts=4 GGGG A.DG4,A.DG12,A.DG16,A.DG22
 2 glyco-bond=-s-- groove=wn-- planarity=0.079 type=planar nts=4 GGGG A.DG5,A.DG11,A.DG17,A.DG23
 3 glyco-bond=-s-- groove=wn-- planarity=0.085 type=planar nts=4 GGGG A.DG6,A.DG10,A.DG18,A.DG24

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=s-ss groove=wn-- Major-->WC nts=4 GGGG A.DG4,A.DG12,A.DG16,A.DG22
 2  glyco-bond=-s-- groove=wn-- WC-->Major nts=4 GGGG A.DG5,A.DG11,A.DG17,A.DG23
 3  glyco-bond=-s-- groove=wn-- WC-->Major nts=4 GGGG A.DG6,A.DG10,A.DG18,A.DG24
  step#1  mm(<>,outward)  area=10.22 rise=3.44 twist=24.0
  step#2  pm(>>,forward)  area=16.90 rise=3.72 twist=22.7
  strand#1 DNA glyco-bond=s-- nts=3 GGG A.DG4,A.DG5,A.DG6
  strand#2 DNA glyco-bond=-ss nts=3 GGG A.DG12,A.DG11,A.DG10
  strand#3 DNA glyco-bond=s-- nts=3 GGG A.DG16,A.DG17,A.DG18
  strand#4 DNA glyco-bond=s-- nts=3 GGG A.DG22,A.DG23,A.DG24

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2 stacking diagrams
 1  glyco-bond=s-ss groove=wn-- Major-->WC nts=4 GGGG A.DG4,A.DG12,A.DG16,A.DG22
2 glyco-bond=-s-- groove=wn-- WC-->Major nts=4 GGGG A.DG5,A.DG11,A.DG17,A.DG23
step#1 mm(<>,outward) area=10.22 rise=3.44 twist=24.0

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 2  glyco-bond=-s-- groove=wn-- WC-->Major nts=4 GGGG A.DG5,A.DG11,A.DG17,A.DG23
3 glyco-bond=-s-- groove=wn-- WC-->Major nts=4 GGGG A.DG6,A.DG10,A.DG18,A.DG24
step#2 pm(>>,forward) area=16.90 rise=3.72 twist=22.7

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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, UDUU, anti-parallel, 3(-Lw-Ln-P), hybrid-2(3+1)

 1  glyco-bond=s-ss groove=wn-- Major-->WC nts=4 GGGG A.DG4,A.DG12,A.DG16,A.DG22
 2  glyco-bond=-s-- groove=wn-- WC-->Major nts=4 GGGG A.DG5,A.DG11,A.DG17,A.DG23
 3  glyco-bond=-s-- groove=wn-- WC-->Major nts=4 GGGG A.DG6,A.DG10,A.DG18,A.DG24
  step#1  mm(<>,outward)  area=10.22 rise=3.44 twist=24.0
  step#2  pm(>>,forward)  area=16.90 rise=3.72 twist=22.7
  strand#1  U DNA glyco-bond=s-- nts=3 GGG A.DG4,A.DG5,A.DG6
  strand#2  D DNA glyco-bond=-ss nts=3 GGG A.DG12,A.DG11,A.DG10
  strand#3  U DNA glyco-bond=s-- nts=3 GGG A.DG16,A.DG17,A.DG18
  strand#4  U DNA glyco-bond=s-- nts=3 GGG A.DG22,A.DG23,A.DG24
  loop#1 type=lateral   strands=[#1,#2] nts=3 TTA A.DT7,A.DT8,A.DA9
  loop#2 type=lateral   strands=[#2,#3] nts=3 TTA A.DT13,A.DT14,A.DA15
  loop#3 type=propeller strands=[#3,#4] nts=3 TTA A.DT19,A.DT20,A.DA21

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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)