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

PDB-id
2l7v
Class
DNA-inhibitor
Method
NMR
Summary
Quindoline-G-quadruplex complex
Reference
Dai, J., Carver, M., Hurley, L.H., Yang, D.: (2011) "Solution Structure of a 2:1 Quindoline-c-MYC G-Quadruplex: Insights into G-Quadruplex-Interactive Small Molecule Drug Design." J.Am.Chem.Soc., 133, 17673-17680.
Abstract
Unimolecular parallel-stranded G-quadruplex structures are found to be prevalent in gene promoters. The nuclease hypersensitivity element III(1) (NHE III(1)) of the c-MYC promoter can form transcriptionally active and silenced forms, and the formation of DNA G-quadruplex structures has been shown to be critical for c-MYC transcriptional silencing. The solution structure of a 2:1 quindoline-G-quadruplex complex has been solved and shows unexpected features, including the drug-induced reorientation of the flanking sequences to form a new binding pocket. While both 3' and 5' complexes show overall similar features, there are identifiable differences that emphasize the importance of both stacking and electronic interactions. For the first time, we describe the importance of the shape of the ligand as well as the two flanking bases in determining drug binding specificity. These structures provide important insights for the structure-based rational design of drugs that bind to unimolecular parallel G-quadruplexes commonly found in promoter elements.
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]

PyMOL session file PDB file View in 3Dmol.js

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

 1 glyco-bond=---- groove=---- planarity=0.146 type=planar nts=4 GGGG A.DG7,A.DG11,A.DG16,A.DG20
 2 glyco-bond=---- groove=---- planarity=0.163 type=other  nts=4 GGGG A.DG8,A.DG12,A.DG17,A.DG21
 3 glyco-bond=---- groove=---- planarity=0.178 type=other  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=10.72 rise=3.39 twist=30.5
  step#2  pm(>>,forward)  area=14.90 rise=3.32 twist=26.8
  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=10.72 rise=3.39 twist=30.5

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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=14.90 rise=3.32 twist=26.8

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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=10.72 rise=3.39 twist=30.5
  step#2  pm(>>,forward)  area=14.90 rise=3.32 twist=26.8
  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)