Summary information and primary citation

PDB-id
3qsf
Class
DNA
Method
X-ray (2.4 Å)
Summary
The first crystal structure of a human telomeric g-quadruplex DNA bound to a metal-containing ligand (a nickel complex)
Reference
Campbell NH, Karim NH, Parkinson GN, Gunaratnam M, Petrucci V, Todd AK, Vilar R, Neidle S (2012): "Molecular basis of structure-activity relationships between salphen metal complexes and human telomeric DNA quadruplexes." J.Med.Chem., 55, 209-222. doi: 10.1021/jm201140v.
Abstract
The first X-ray crystal structures of nickel(II) and copper(II) salphen metal complexes bound to a quadruplex DNA are presented. Two structures have been determined and show that these salphen-metal complexes bind to human telomeric quadruplexes by end-stacking, with the metal in each case almost in line with the potassium ion channel. Quadruplex and duplex DNA binding is presented for these two and other related salphen complexes, all with side-chains terminating in pyrrolidino end-groups and differing patterns of substitution on the salphen core. The crystal structures are able to provide rationalizations for the structure-activity data, and in particular for the superior quadruplex-binding of the nickel complexes compared to that of the copper-containing ones. The complexes show significant antiproliferative activity for the compounds in a panel of cancer cell lines. They also show telomerase inhibitory activity in the telomerase TRAP-LIG assay.
G4 notes
3 G-tetrads, 1 G4 helix, 1 G4 stem, UUUU, parallel, 4+0

Cartoon-block schematics in six views (download the tarball)

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List of 3 G-tetrads

 1 glyco-bond=---- sugar=3-3- groove=---- planarity=0.366 type=bowl-2 -- nts=4 GGGG 1:X.DG1002,1:X.DG1008,2:X.DG1002,2:X.DG1008
 2 glyco-bond=---- sugar=3-3- groove=---- planarity=0.270 type=saddle -- nts=4 GGGG 1:X.DG1003,1:X.DG1009,2:X.DG1003,2:X.DG1009
 3 glyco-bond=---- sugar=---- groove=---- planarity=0.274 type=bowl   -- nts=4 GGGG 1:X.DG1004,1:X.DG1010,2:X.DG1004,2:X.DG1010

List of 1 G4-helix

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-tetrads, inter-molecular, with 1 stem
 1  glyco-bond=---- sugar=3-3- groove=---- WC-->Major -- nts=4 GGGG 1:X.DG1002,1:X.DG1008,2:X.DG1002,2:X.DG1008
 2  glyco-bond=---- sugar=3-3- groove=---- WC-->Major -- nts=4 GGGG 1:X.DG1003,1:X.DG1009,2:X.DG1003,2:X.DG1009
 3  glyco-bond=---- sugar=---- groove=---- WC-->Major -- nts=4 GGGG 1:X.DG1004,1:X.DG1010,2:X.DG1004,2:X.DG1010
  step#1  pm(>>,forward)  area=10.32 rise=3.32 twist=33.4
  step#2  pm(>>,forward)  area=14.37 rise=3.61 twist=25.1
  strand#1 DNA glyco-bond=--- sugar=33- nts=3 GGG 1:X.DG1002,1:X.DG1003,1:X.DG1004
  strand#2 DNA glyco-bond=--- sugar=--- nts=3 GGG 1:X.DG1008,1:X.DG1009,1:X.DG1010
  strand#3 DNA glyco-bond=--- sugar=33- nts=3 GGG 2:X.DG1002,2:X.DG1003,2:X.DG1004
  strand#4 DNA glyco-bond=--- sugar=--- nts=3 GGG 2:X.DG1008,2:X.DG1009,2:X.DG1010

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2 stacking diagrams 
 1  glyco-bond=---- sugar=3-3- groove=---- WC-->Major -- nts=4 GGGG 1:X.DG1002,1:X.DG1008,2:X.DG1002,2:X.DG1008
 2  glyco-bond=---- sugar=3-3- groove=---- WC-->Major -- nts=4 GGGG 1:X.DG1003,1:X.DG1009,2:X.DG1003,2:X.DG1009
  step#1  pm(>>,forward)  area=10.32 rise=3.32 twist=33.4

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 2  glyco-bond=---- sugar=3-3- groove=---- WC-->Major -- nts=4 GGGG 1:X.DG1003,1:X.DG1009,2:X.DG1003,2:X.DG1009
 3  glyco-bond=---- sugar=---- groove=---- WC-->Major -- nts=4 GGGG 1:X.DG1004,1:X.DG1010,2:X.DG1004,2:X.DG1010
  step#2  pm(>>,forward)  area=14.37 rise=3.61 twist=25.1

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List of 1 G4-stem

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-tetrads, 2 loops, inter-molecular, UUUU, parallel, 4+0
 1  glyco-bond=---- sugar=3-3- groove=---- WC-->Major -- nts=4 GGGG 1:X.DG1002,1:X.DG1008,2:X.DG1002,2:X.DG1008
 2  glyco-bond=---- sugar=3-3- groove=---- WC-->Major -- nts=4 GGGG 1:X.DG1003,1:X.DG1009,2:X.DG1003,2:X.DG1009
 3  glyco-bond=---- sugar=---- groove=---- WC-->Major -- nts=4 GGGG 1:X.DG1004,1:X.DG1010,2:X.DG1004,2:X.DG1010
  step#1  pm(>>,forward)  area=10.32 rise=3.32 twist=33.4
  step#2  pm(>>,forward)  area=14.37 rise=3.61 twist=25.1
  strand#1  U DNA glyco-bond=--- sugar=33- nts=3 GGG 1:X.DG1002,1:X.DG1003,1:X.DG1004
  strand#2  U DNA glyco-bond=--- sugar=--- nts=3 GGG 1:X.DG1008,1:X.DG1009,1:X.DG1010
  strand#3  U DNA glyco-bond=--- sugar=33- nts=3 GGG 2:X.DG1002,2:X.DG1003,2:X.DG1004
  strand#4  U DNA glyco-bond=--- sugar=--- nts=3 GGG 2:X.DG1008,2:X.DG1009,2:X.DG1010
  loop#1 type=propeller strands=[#1,#2] nts=3 TTA 1:X.DT1005,1:X.DT1006,1:X.DA1007
  loop#2 type=propeller strands=[#3,#4] nts=3 TTA 2:X.DT1005,2:X.DT1006,2:X.DA1007

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