Summary information and primary citation

PDB-id
5z80
Class
DNA
Method
NMR
Summary
Solution structure for the 1:1 complex of a platinum(ii)-based tripod bound to a hybrid-1 human telomeric g-quadruplex
Reference
Liu W, Zhong YF, Liu LY, Shen CT, Zeng W, Wang F, Yang D, Mao ZW (2018): "Solution structures of multiple G-quadruplex complexes induced by a platinum(II)-based tripod reveal dynamic binding." Nat Commun, 9, 3496. doi: 10.1038/s41467-018-05810-4.
Abstract
DNA G-quadruplexes are not only attractive drug targets for cancer therapeutics, but also have important applications in supramolecular assembly. Here, we report a platinum(II)-based tripod (Pt-tripod) specifically binds the biological relevant hybrid-1 human telomeric G-quadruplex (Tel26), and strongly inhibits telomerase activity. Further investigations illustrate Pt-tripod induces the formation of monomeric and multimeric Pt-tripod‒Tel26 complex structures in solution. We solve the 1:1 and the unique dimeric 4:2 Pt-tripod-Tel26 complex structures by NMR. The structures indicate preferential binding of Pt-tripod to the 5'-end of Tel26 at a low Pt-tripod/Tel26 ratio of 0-1.0. After adding more Pt-tripod, the Pt-tripod binds the 3'-end of Tel26, unexpectedly inducing a unique dimeric 4:2 structure interlocked by an A:A non-canonical pair at the 3'-end. Our structures provide a structural basis for understanding the dynamic binding of small molecules with G-quadruplex and DNA damage mechanisms, and insights into the recognition and assembly of higher-order G-quadruplexes.
G4 notes
3 G-tetrads, 1 G4 helix, 1 G4 stem, UUDU, hybrid1, 3+1, 3(-P-Lw-Ln)

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

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List of 3 G-tetrads

 1 glyco-bond=-s-s sugar=--.- groove=wnwn planarity=0.357 type=other  O- nts=4 GGGG A.DG4,A.DG22,A.DG18,A.DG10
 2 glyco-bond=--s- sugar=-.-- groove=-wn- planarity=0.255 type=other  O+ nts=4 GGGG A.DG5,A.DG11,A.DG17,A.DG23
 3 glyco-bond=--s- sugar=-.-3 groove=-wn- planarity=0.250 type=other  O+ nts=4 GGGG A.DG6,A.DG12,A.DG16,A.DG24

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, INTRA-molecular, with 1 stem
 1  glyco-bond=-s-s sugar=--.- groove=wnwn WC-->Major O- nts=4 GGGG A.DG4,A.DG22,A.DG18,A.DG10
 2  glyco-bond=--s- sugar=---. groove=-nw- Major-->WC O+ nts=4 GGGG A.DG5,A.DG23,A.DG17,A.DG11
 3  glyco-bond=--s- sugar=-3-. groove=-nw- Major-->WC O+ nts=4 GGGG A.DG6,A.DG24,A.DG16,A.DG12
  step#1  mm(<>,outward)  area=12.33 rise=3.69 twist=21.8
  step#2  pm(>>,forward)  area=13.21 rise=3.58 twist=28.2
  strand#1 DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG4,A.DG5,A.DG6
  strand#2 DNA glyco-bond=s-- sugar=--3 nts=3 GGG A.DG22,A.DG23,A.DG24
  strand#3 DNA glyco-bond=-ss sugar=.-- nts=3 GGG A.DG18,A.DG17,A.DG16
  strand#4 DNA glyco-bond=s-- sugar=-.. nts=3 GGG A.DG10,A.DG11,A.DG12

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2 stacking diagrams 
 1  glyco-bond=-s-s sugar=--.- groove=wnwn WC-->Major O- nts=4 GGGG A.DG4,A.DG22,A.DG18,A.DG10
 2  glyco-bond=--s- sugar=---. groove=-nw- Major-->WC O+ nts=4 GGGG A.DG5,A.DG23,A.DG17,A.DG11
  step#1  mm(<>,outward)  area=12.33 rise=3.69 twist=21.8

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 2  glyco-bond=--s- sugar=---. groove=-nw- Major-->WC O+ nts=4 GGGG A.DG5,A.DG23,A.DG17,A.DG11
 3  glyco-bond=--s- sugar=-3-. groove=-nw- Major-->WC O+ nts=4 GGGG A.DG6,A.DG24,A.DG16,A.DG12
  step#2  pm(>>,forward)  area=13.21 rise=3.58 twist=28.2

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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, 3 loops, INTRA-molecular, UUDU, hybrid1, WARNING, 3+1, 3(-P-Lw-Ln), WARNING
 1  glyco-bond=-s-s sugar=--.- groove=nwnw Major-->WC O- nts=4 GGGG A.DG4,A.DG10,A.DG18,A.DG22
 2  glyco-bond=--s- sugar=-.-- groove=-wn- WC-->Major O+ nts=4 GGGG A.DG5,A.DG11,A.DG17,A.DG23
 3  glyco-bond=--s- sugar=-.-3 groove=-wn- WC-->Major O+ nts=4 GGGG A.DG6,A.DG12,A.DG16,A.DG24
  step#1  mm(<>,outward)  area=12.33 rise=3.69 twist=21.8
  step#2  pm(>>,forward)  area=13.21 rise=3.58 twist=28.2
  strand#1  U DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG4,A.DG5,A.DG6
  strand#2  U DNA glyco-bond=s-- sugar=-.. nts=3 GGG A.DG10,A.DG11,A.DG12
  strand#3  D DNA glyco-bond=-ss sugar=.-- nts=3 GGG A.DG18,A.DG17,A.DG16
  strand#4  U DNA glyco-bond=s-- sugar=--3 nts=3 GGG A.DG22,A.DG23,A.DG24
  loop#1 type=propeller 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=lateral   strands=[#3,#4] nts=3 TTA A.DT19,A.DT20,A.DA21

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