DSSR-enabled G4 identification/annotation

Summary information and primary citation

PDB-id: 5z8f
Class: DNA
Method: NMR
Summary: Solution structure for the unique dimeric 4:2 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: 6 G-tetrads, 2 G4 helices, 2 G4 stems, UUDU, hybrid1, 3+1, 3(-P-Lw-Ln)

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

List of 6 G-tetrads

 1 glyco-bond=ss-s sugar=--.- groove=-wn- planarity=0.407 type=saddle O- nts=4 GGGG A.DG4,A.DG10,A.DG18,A.DG22
 2 glyco-bond=--s- sugar=..-- groove=-wn- planarity=0.348 type=other  O+ nts=4 GGGG A.DG5,A.DG11,A.DG17,A.DG23
 3 glyco-bond=--s- sugar=-3-. groove=-wn- planarity=0.297 type=bowl-2 O+ nts=4 GGGG A.DG6,A.DG12,A.DG16,A.DG24
 4 glyco-bond=ss-s sugar=---- groove=-wn- planarity=0.354 type=saddle O- nts=4 GGGG B.DG4,B.DG10,B.DG18,B.DG22
 5 glyco-bond=--s- sugar=..-- groove=-wn- planarity=0.272 type=other  O+ nts=4 GGGG B.DG5,B.DG11,B.DG17,B.DG23
 6 glyco-bond=--s- sugar=-3-3 groove=-wn- planarity=0.214 type=bowl-2 O+ nts=4 GGGG B.DG6,B.DG12,B.DG16,B.DG24

List of 2 G4-helices

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=ss-s sugar=--.- groove=-wn- 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=11.08 rise=3.64 twist=18.8 step#2 pm(>>,forward) area=14.89 rise=3.57 twist=23.0 strand#1 DNA glyco-bond=s-- sugar=-.- nts=3 GGG A.DG4,A.DG5,A.DG6 strand#2 DNA glyco-bond=s-- sugar=-.3 nts=3 GGG A.DG10,A.DG11,A.DG12 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.DG22,A.DG23,A.DG24 Download PDB file Interactive view in 3Dmol.js
2 stacking diagrams
	1 glyco-bond=ss-s sugar=--.- groove=-wn- 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 step#1 mm(<>,outward) area=11.08 rise=3.64 twist=18.8 Download PDB file Interactive view in 3Dmol.js
	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#2 pm(>>,forward) area=14.89 rise=3.57 twist=23.0 Download PDB file Interactive view in 3Dmol.js

Helix#2, 3 G-tetrads, INTRA-molecular, with 1 stem

	1 glyco-bond=ss-s sugar=---- groove=-wn- Major-->WC O- nts=4 GGGG B.DG4,B.DG10,B.DG18,B.DG22 2 glyco-bond=--s- sugar=..-- groove=-wn- WC-->Major O+ nts=4 GGGG B.DG5,B.DG11,B.DG17,B.DG23 3 glyco-bond=--s- sugar=-3-3 groove=-wn- WC-->Major O+ nts=4 GGGG B.DG6,B.DG12,B.DG16,B.DG24 step#1 mm(<>,outward) area=10.22 rise=3.66 twist=20.3 step#2 pm(>>,forward) area=16.43 rise=3.58 twist=21.6 strand#1 DNA glyco-bond=s-- sugar=-.- nts=3 GGG B.DG4,B.DG5,B.DG6 strand#2 DNA glyco-bond=s-- sugar=-.3 nts=3 GGG B.DG10,B.DG11,B.DG12 strand#3 DNA glyco-bond=-ss sugar=--- nts=3 GGG B.DG18,B.DG17,B.DG16 strand#4 DNA glyco-bond=s-- sugar=--3 nts=3 GGG B.DG22,B.DG23,B.DG24 Download PDB file Interactive view in 3Dmol.js
2 stacking diagrams
	1 glyco-bond=ss-s sugar=---- groove=-wn- Major-->WC O- nts=4 GGGG B.DG4,B.DG10,B.DG18,B.DG22 2 glyco-bond=--s- sugar=..-- groove=-wn- WC-->Major O+ nts=4 GGGG B.DG5,B.DG11,B.DG17,B.DG23 step#1 mm(<>,outward) area=10.22 rise=3.66 twist=20.3 Download PDB file Interactive view in 3Dmol.js
	2 glyco-bond=--s- sugar=..-- groove=-wn- WC-->Major O+ nts=4 GGGG B.DG5,B.DG11,B.DG17,B.DG23 3 glyco-bond=--s- sugar=-3-3 groove=-wn- WC-->Major O+ nts=4 GGGG B.DG6,B.DG12,B.DG16,B.DG24 step#2 pm(>>,forward) area=16.43 rise=3.58 twist=21.6 Download PDB file Interactive view in 3Dmol.js

List of 2 G4-stems

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, 3+1, 3(-P-Lw-Ln)

 1  glyco-bond=ss-s sugar=--.- groove=-wn- 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=11.08 rise=3.64 twist=18.8
  step#2  pm(>>,forward)  area=14.89 rise=3.57 twist=23.0
  strand#1  U DNA glyco-bond=s-- sugar=-.- nts=3 GGG A.DG4,A.DG5,A.DG6
  strand#2  U DNA glyco-bond=s-- sugar=-.3 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=--. 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

Download PDB file
Interactive view in 3Dmol.js

Stem#2, 3 G-tetrads, 3 loops, INTRA-molecular, UUDU, hybrid1, 3+1, 3(-P-Lw-Ln)

 1  glyco-bond=ss-s sugar=---- groove=-wn- Major-->WC O- nts=4 GGGG B.DG4,B.DG10,B.DG18,B.DG22
 2  glyco-bond=--s- sugar=..-- groove=-wn- WC-->Major O+ nts=4 GGGG B.DG5,B.DG11,B.DG17,B.DG23
 3  glyco-bond=--s- sugar=-3-3 groove=-wn- WC-->Major O+ nts=4 GGGG B.DG6,B.DG12,B.DG16,B.DG24
  step#1  mm(<>,outward)  area=10.22 rise=3.66 twist=20.3
  step#2  pm(>>,forward)  area=16.43 rise=3.58 twist=21.6
  strand#1  U DNA glyco-bond=s-- sugar=-.- nts=3 GGG B.DG4,B.DG5,B.DG6
  strand#2  U DNA glyco-bond=s-- sugar=-.3 nts=3 GGG B.DG10,B.DG11,B.DG12
  strand#3  D DNA glyco-bond=-ss sugar=--- nts=3 GGG B.DG18,B.DG17,B.DG16
  strand#4  U DNA glyco-bond=s-- sugar=--3 nts=3 GGG B.DG22,B.DG23,B.DG24
  loop#1 type=propeller strands=[#1,#2] nts=3 TTA B.DT7,B.DT8,B.DA9
  loop#2 type=lateral   strands=[#2,#3] nts=3 TTA B.DT13,B.DT14,B.DA15
  loop#3 type=lateral   strands=[#3,#4] nts=3 TTA B.DT19,B.DT20,B.DA21