Summary information and primary citation

PDB-id
2mco
Class
DNA
Method
NMR
Summary
Structural studies on dinuclear ruthenium(ii) complexes that bind diastereoselectively to an anti-parallel folded human telomere sequence
Reference
Wilson T, Costa PJ, Felix V, Williamson MP, Thomas JA (2013): "Structural Studies on Dinuclear Ruthenium(II) Complexes That Bind Diastereoselectively to an Antiparallel Folded Human Telomere Sequence." J.Med.Chem., 56, 8674-8683. doi: 10.1021/jm401119b.
Abstract
We report DNA binding studies of the dinuclear ruthenium ligand [{Ru(phen)2}2tpphz](4+) in enantiomerically pure forms. As expected from previous studies of related complexes, both isomers bind with similar affinity to B-DNA and have enhanced luminescence. However, when tested against the G-quadruplex from human telomeres (which we show to form an antiparallel basket structure with a diagonal loop across one end), the ΛΛ isomer binds approximately 40 times more tightly than the ΔΔ, with a stronger luminescence. NMR studies show that the complex binds at both ends of the quadruplex. Modeling studies, based on experimentally derived restraints obtained for the closely related [{Ru(bipy)2}2tpphz](4+), show that the ΛΛ isomer fits neatly under the diagonal loop, whereas the ΔΔ isomer is unable to bind here and binds at the lateral loop end. Molecular dynamics simulations show that the ΔΔ isomer is prevented from binding under the diagonal loop by the rigidity of the loop. We thus present a novel enantioselective binding substrate for antiparallel basket G-quadruplexes, with features that make it a useful tool for quadruplex studies.
G4 notes
3 G-tetrads, 1 G4 helix, 1 G4 stem, UDDU, anti-parallel:basket, 2+2, 3(-LwD+Ln)

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

PyMOL session file

Download PDB file

View in 3Dmol.js

List of 3 G-tetrads

 1 glyco-bond=-s-- sugar=33-- groove=wn-- planarity=0.851 type=other  N+ nts=4 GGGG A.DG2,A.DG10,A.DG22,A.DG14
 2 glyco-bond=s--s sugar=-.-. groove=w-n- planarity=0.542 type=other  N- nts=4 GGGG A.DG3,A.DG9,A.DG21,A.DG15
 3 glyco-bond=-ss- sugar=--.- groove=w-n- planarity=0.489 type=saddle N+ nts=4 GGGG A.DG4,A.DG8,A.DG20,A.DG16

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-- sugar=33-- groove=wn-- WC-->Major N+ nts=4 GGGG A.DG2,A.DG10,A.DG22,A.DG14
 2  glyco-bond=s--s sugar=-.-. groove=w-n- Major-->WC N- nts=4 GGGG A.DG3,A.DG9,A.DG21,A.DG15
 3  glyco-bond=-ss- sugar=--.- groove=w-n- WC-->Major N+ nts=4 GGGG A.DG4,A.DG8,A.DG20,A.DG16
  step#1  pp(><,inward)   area=22.30 rise=3.60 twist=28.5
  step#2  mm(<>,outward)  area=9.82  rise=3.63 twist=19.2
  strand#1 DNA glyco-bond=-s- sugar=3-- nts=3 GGG A.DG2,A.DG3,A.DG4
  strand#2 DNA glyco-bond=s-s sugar=3.- nts=3 GGG A.DG10,A.DG9,A.DG8
  strand#3 DNA glyco-bond=--s sugar=--. nts=3 GGG A.DG22,A.DG21,A.DG20
  strand#4 DNA glyco-bond=-s- sugar=-.- nts=3 GGG A.DG14,A.DG15,A.DG16

Download PDB file
Interactive view in 3Dmol.js
2 stacking diagrams 
 1  glyco-bond=-s-- sugar=33-- groove=wn-- WC-->Major N+ nts=4 GGGG A.DG2,A.DG10,A.DG22,A.DG14
 2  glyco-bond=s--s sugar=-.-. groove=w-n- Major-->WC N- nts=4 GGGG A.DG3,A.DG9,A.DG21,A.DG15
  step#1  pp(><,inward)   area=22.30 rise=3.60 twist=28.5

Download PDB file
Interactive view in 3Dmol.js

 
 2  glyco-bond=s--s sugar=-.-. groove=w-n- Major-->WC N- nts=4 GGGG A.DG3,A.DG9,A.DG21,A.DG15
 3  glyco-bond=-ss- sugar=--.- groove=w-n- WC-->Major N+ nts=4 GGGG A.DG4,A.DG8,A.DG20,A.DG16
  step#2  mm(<>,outward)  area=9.82  rise=3.63 twist=19.2

Download PDB file
Interactive view in 3Dmol.js

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, UDDU, anti-parallel:basket, WARNING, 2+2, 3(-LwD+Ln), WARNING
 1  glyco-bond=-s-- sugar=33-- groove=wn-- WC-->Major N+ nts=4 GGGG A.DG2,A.DG10,A.DG22,A.DG14
 2  glyco-bond=s--s sugar=-.-. groove=w-n- Major-->WC N- nts=4 GGGG A.DG3,A.DG9,A.DG21,A.DG15
 3  glyco-bond=-ss- sugar=--.- groove=w-n- WC-->Major N+ nts=4 GGGG A.DG4,A.DG8,A.DG20,A.DG16
  step#1  pp(><,inward)   area=22.30 rise=3.60 twist=28.5
  step#2  mm(<>,outward)  area=9.82  rise=3.63 twist=19.2
  strand#1  U DNA glyco-bond=-s- sugar=3-- nts=3 GGG A.DG2,A.DG3,A.DG4
  strand#2  D DNA glyco-bond=s-s sugar=3.- nts=3 GGG A.DG10,A.DG9,A.DG8
  strand#3  D DNA glyco-bond=--s sugar=--. nts=3 GGG A.DG22,A.DG21,A.DG20
  strand#4  U DNA glyco-bond=-s- sugar=-.- nts=3 GGG A.DG14,A.DG15,A.DG16
  loop#1 type=lateral   strands=[#1,#2] nts=3 TTA A.DT5,A.DT6,A.DA7
  loop#2 type=diagonal  strands=[#2,#4] nts=3 TTA A.DT11,A.DT12,A.DA13
  loop#3 type=lateral   strands=[#4,#3] nts=3 TTA A.DT17,A.DT18,A.DA19

Download PDB file
Interactive view in 3Dmol.js