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

PDB-id
6o2l
Class
DNA
Method
NMR
Summary
NMR structure of the 2:1 complex of a carbazole derivative bmvc bound to c-myc G-quadruplex
Reference
Liu, W., Lin, C., Wu, G., Dai, J., Chang, T.C., Yang, D.: (2019) "Structures of 1:1 and 2:1 complexes of BMVC and MYC promoter G-quadruplex reveal a mechanism of ligand conformation adjustment for G4-recognition." Nucleic Acids Res., 47, 11931-11942.
Abstract
BMVC is the first fluorescent probe designed to detect G-quadruplexes (G4s) in vivo. The MYC oncogene promoter forms a G4 (MycG4) which acts as a transcription silencer. Here, we report the high-affinity and specific binding of BMVC to MycG4 with unusual slow-exchange rates on the NMR timescale. We also show that BMVC represses MYC in cancer cells. We determined the solution structures of the 1:1 and 2:1 BMVC-MycG4 complexes. BMVC first binds the 5'-end of MycG4 to form a 1:1 complex with a well-defined structure. At higher ratio, BMVC also binds the 3'-end to form a second complex. In both complexes, the crescent-shaped BMVC recruits a flanking DNA residue to form a BMVC-base plane stacking over the external G-tetrad. Remarkably, BMVC adjusts its conformation to a contracted form to match the G-tetrad for an optimal stacking interaction. This is the first structural example showing the importance of ligand conformational adjustment in G4 recognition. BMVC binds the more accessible 5'-end with higher affinity, whereas sequence specificity is present at the weaker-binding 3'-site. Our structures provide insights into specific recognition of MycG4 by BMVC and useful information for design of G4-targeted anticancer drugs and fluorescent probes.
G4 notes
3 G-tetrads, 1 G4 helix, 1 G4 stem · 3(-P-P-P), parallel(4+0), UUUU

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

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

 1 glyco-bond=---- groove=---- planarity=0.166 type=other  nts=4 GGGG A.DG7,A.DG11,A.DG16,A.DG20
 2 glyco-bond=---- groove=---- planarity=0.094 type=planar nts=4 GGGG A.DG8,A.DG12,A.DG17,A.DG21
 3 glyco-bond=---- groove=---- planarity=0.094 type=planar nts=4 GGGG A.DG9,A.DG13,A.DG18,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=---- groove=---- WC-->Major nts=4 GGGG A.DG7,A.DG11,A.DG16,A.DG20
 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG8,A.DG12,A.DG17,A.DG21
 3  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG9,A.DG13,A.DG18,A.DG22
  step#1  pm(>>,forward)  area=7.78  rise=3.59 twist=33.2
  step#2  pm(>>,forward)  area=14.30 rise=3.83 twist=25.3
  strand#1 DNA glyco-bond=--- nts=3 GGG A.DG7,A.DG8,A.DG9
  strand#2 DNA glyco-bond=--- nts=3 GGG A.DG11,A.DG12,A.DG13
  strand#3 DNA glyco-bond=--- nts=3 GGG A.DG16,A.DG17,A.DG18
  strand#4 DNA glyco-bond=--- nts=3 GGG A.DG20,A.DG21,A.DG22

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2 stacking diagrams
 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG7,A.DG11,A.DG16,A.DG20
2 glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG8,A.DG12,A.DG17,A.DG21
step#1 pm(>>,forward) area=7.78 rise=3.59 twist=33.2

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 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG8,A.DG12,A.DG17,A.DG21
3 glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG9,A.DG13,A.DG18,A.DG22
step#2 pm(>>,forward) area=14.30 rise=3.83 twist=25.3

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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, 3 loops, INTRA-molecular, UUUU, parallel, 3(-P-P-P), parallel(4+0)

 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG7,A.DG11,A.DG16,A.DG20
 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG8,A.DG12,A.DG17,A.DG21
 3  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG9,A.DG13,A.DG18,A.DG22
  step#1  pm(>>,forward)  area=7.78  rise=3.59 twist=33.2
  step#2  pm(>>,forward)  area=14.30 rise=3.83 twist=25.3
  strand#1  U DNA glyco-bond=--- nts=3 GGG A.DG7,A.DG8,A.DG9
  strand#2  U DNA glyco-bond=--- nts=3 GGG A.DG11,A.DG12,A.DG13
  strand#3  U DNA glyco-bond=--- nts=3 GGG A.DG16,A.DG17,A.DG18
  strand#4  U DNA glyco-bond=--- nts=3 GGG A.DG20,A.DG21,A.DG22
  loop#1 type=propeller strands=[#1,#2] nts=1 T A.DT10
  loop#2 type=propeller strands=[#2,#3] nts=2 TA A.DT14,A.DA15
  loop#3 type=propeller strands=[#3,#4] nts=1 T A.DT19

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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)