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

PDB-id
2kyo
Class
DNA
Method
NMR
Summary
Dimeric human ckit-2 proto-oncogene promoter quadruplex DNA NMR, 10 structures
Reference
Kuryavyi, V., Phan, A.T., Patel, D.J.: (2010) "Solution structures of all parallel-stranded monomeric and dimeric G-quadruplex scaffolds of the human c-kit2 promoter." Nucleic Acids Res., 38, 6757-6773.
Abstract
Previous studies have demonstrated that nuclease hypersensitivity regions of several proto-oncogenic DNA promoters, situated upstream of transcription start sites, contain guanine-rich tracts that form intramolecular G-quadruplexes stabilized by stacked G•G•G•G tetrads in monovalent cation solution. The human c-kit oncogenic promoter, an important target in the treatment of gastrointestinal tumors, contains two such stretches of guanine-rich tracts, designated c-kit1 and c-kit2. Our previous nuclear magnetic resonance (NMR)-based studies reported on the novel G-quadruplex scaffold of the c-kit1 promoter in K(+)-containing solution, where we showed for the first time that even an isolated guanine was involved in G-tetrad formation. These NMR-based studies are now extended to the c-kit2 promoter, which adopts two distinct all-parallel-stranded conformations in slow exchange, one of which forms a monomeric G-quadruplex (form-I) in 20 mM K(+)-containing solution and the other a novel dimeric G-quadruplex (form-II) in 100 mM K(+)-containing solution. The c-kit2 promoter dimeric form-II G-quadruplex adopts an unprecedented all-parallel-stranded topology where individual c-kit2 promoter strands span a pair of three-G-tetrad-layer-containing all-parallel-stranded G-quadruplexes aligned in a 3' to 5'-end orientation, with stacking continuity between G-quadruplexes mediated by a sandwiched A•A non-canonical pair. We propose that strand exchange during recombination events within guanine-rich segments, could potentially be mediated by a synapsis intermediate involving an intergenic parallel-stranded dimeric G-quadruplex.
G4 notes
6 G-tetrads, 2 G4 helices, 2 G4 stems · 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 6 G-tetrads [summary · schematics · helices · stems · costacks · homepage]

 1 glyco-bond=---- groove=---- planarity=0.044 type=planar nts=4 GGGG A.DG2,A.DG6,B.DG2,B.DG6
 2 glyco-bond=---- groove=---- planarity=0.065 type=planar nts=4 GGGG A.DG3,A.DG7,B.DG3,B.DG7
 3 glyco-bond=---- groove=---- planarity=0.140 type=planar nts=4 GGGG A.DG4,A.DG8,B.DG4,B.DG8
 4 glyco-bond=---- groove=---- planarity=0.106 type=planar nts=4 GGGG A.DG14,A.DG18,B.DG14,B.DG18
 5 glyco-bond=---- groove=---- planarity=0.051 type=planar nts=4 GGGG A.DG15,A.DG19,B.DG15,B.DG19
 6 glyco-bond=---- groove=---- planarity=0.179 type=other  nts=4 GGGG A.DG16,A.DG20,B.DG16,B.DG20

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, 3 G-tetrad layers, inter-molecular, with 1 stem

 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG2,A.DG6,B.DG2,B.DG6
 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG7,B.DG3,B.DG7
 3  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG4,A.DG8,B.DG4,B.DG8
  step#1  pm(>>,forward)  area=10.69 rise=3.18 twist=30.8
  step#2  pm(>>,forward)  area=10.39 rise=3.21 twist=31.8
  strand#1 DNA glyco-bond=--- nts=3 GGG A.DG2,A.DG3,A.DG4
  strand#2 DNA glyco-bond=--- nts=3 GGG A.DG6,A.DG7,A.DG8
  strand#3 DNA glyco-bond=--- nts=3 GGG B.DG2,B.DG3,B.DG4
  strand#4 DNA glyco-bond=--- nts=3 GGG B.DG6,B.DG7,B.DG8

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2 stacking diagrams
 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG2,A.DG6,B.DG2,B.DG6
2 glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG7,B.DG3,B.DG7
step#1 pm(>>,forward) area=10.69 rise=3.18 twist=30.8

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 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG7,B.DG3,B.DG7
3 glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG4,A.DG8,B.DG4,B.DG8
step#2 pm(>>,forward) area=10.39 rise=3.21 twist=31.8

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Helix#2, 3 G-tetrad layers, inter-molecular, with 1 stem

 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG14,A.DG18,B.DG14,B.DG18
 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG15,A.DG19,B.DG15,B.DG19
 3  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG16,A.DG20,B.DG16,B.DG20
  step#1  pm(>>,forward)  area=10.23 rise=3.28 twist=31.2
  step#2  pm(>>,forward)  area=14.20 rise=3.29 twist=24.9
  strand#1 DNA glyco-bond=--- nts=3 GGG A.DG14,A.DG15,A.DG16
  strand#2 DNA glyco-bond=--- nts=3 GGG A.DG18,A.DG19,A.DG20
  strand#3 DNA glyco-bond=--- nts=3 GGG B.DG14,B.DG15,B.DG16
  strand#4 DNA glyco-bond=--- nts=3 GGG B.DG18,B.DG19,B.DG20

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2 stacking diagrams
 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG14,A.DG18,B.DG14,B.DG18
2 glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG15,A.DG19,B.DG15,B.DG19
step#1 pm(>>,forward) area=10.23 rise=3.28 twist=31.2

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 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG15,A.DG19,B.DG15,B.DG19
3 glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG16,A.DG20,B.DG16,B.DG20
step#2 pm(>>,forward) area=14.20 rise=3.29 twist=24.9

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List of 2 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, 2 loops, inter-molecular, UUUU, parallel, parallel(4+0)

 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG2,A.DG6,B.DG2,B.DG6
 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG7,B.DG3,B.DG7
 3  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG4,A.DG8,B.DG4,B.DG8
  step#1  pm(>>,forward)  area=10.69 rise=3.18 twist=30.8
  step#2  pm(>>,forward)  area=10.39 rise=3.21 twist=31.8
  strand#1  U DNA glyco-bond=--- nts=3 GGG A.DG2,A.DG3,A.DG4
  strand#2  U DNA glyco-bond=--- nts=3 GGG A.DG6,A.DG7,A.DG8
  strand#3  U DNA glyco-bond=--- nts=3 GGG B.DG2,B.DG3,B.DG4
  strand#4  U DNA glyco-bond=--- nts=3 GGG B.DG6,B.DG7,B.DG8
  loop#1 type=propeller strands=[#1,#2] nts=1 C A.DC5
  loop#2 type=propeller strands=[#3,#4] nts=1 C B.DC5

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

 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG14,A.DG18,B.DG14,B.DG18
 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG15,A.DG19,B.DG15,B.DG19
 3  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG16,A.DG20,B.DG16,B.DG20
  step#1  pm(>>,forward)  area=10.23 rise=3.28 twist=31.2
  step#2  pm(>>,forward)  area=14.20 rise=3.29 twist=24.9
  strand#1  U DNA glyco-bond=--- nts=3 GGG A.DG14,A.DG15,A.DG16
  strand#2  U DNA glyco-bond=--- nts=3 GGG A.DG18,A.DG19,A.DG20
  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.DG18,B.DG19,B.DG20
  loop#1 type=propeller strands=[#1,#2] nts=1 A A.DA17
  loop#2 type=propeller strands=[#3,#4] nts=1 A B.DA17

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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)