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

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, P.J., Felix, V., Williamson, M.P., Thomas, J.A.: (2013) "Structural Studies on Dinuclear Ruthenium(II) Complexes That Bind Diastereoselectively to an Antiparallel Folded Human Telomere Sequence." J.Med.Chem., 56, 8674-8683.
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 · 3(-LwD+Ln), basket(2+2), UDDU

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

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=-s.- groove=w..- WC-->Major nts=4 GGGG A.DG2,A.DG10,A.DG22,A.DG14
 2  glyco-bond=s--s groove=w-n- Major-->WC nts=4 GGGG A.DG3,A.DG9,A.DG21,A.DG15
 3  glyco-bond=-ss- groove=w-n- WC-->Major 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- nts=3 GGG A.DG2,A.DG3,A.DG4
  strand#2 DNA glyco-bond=s-s nts=3 GGG A.DG10,A.DG9,A.DG8
  strand#3 DNA glyco-bond=.-s nts=3 GGG A.DG22,A.DG21,A.DG20
  strand#4 DNA glyco-bond=-s- nts=3 GGG A.DG14,A.DG15,A.DG16

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2 stacking diagrams
 1  glyco-bond=-s.- groove=w..- WC-->Major nts=4 GGGG A.DG2,A.DG10,A.DG22,A.DG14
2 glyco-bond=s--s groove=w-n- Major-->WC nts=4 GGGG A.DG3,A.DG9,A.DG21,A.DG15
step#1 pp(><,inward) area=22.30 rise=3.60 twist=28.5

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

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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, UDDU, anti-parallel, 3(-LwD+Ln), basket(2+2)

 1  glyco-bond=-s.- groove=w..- WC-->Major nts=4 GGGG A.DG2,A.DG10,A.DG22,A.DG14
 2  glyco-bond=s--s groove=w-n- Major-->WC nts=4 GGGG A.DG3,A.DG9,A.DG21,A.DG15
 3  glyco-bond=-ss- groove=w-n- WC-->Major 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- nts=3 GGG A.DG2,A.DG3,A.DG4
  strand#2  D DNA glyco-bond=s-s nts=3 GGG A.DG10,A.DG9,A.DG8
  strand#3  D DNA glyco-bond=.-s nts=3 GGG A.DG22,A.DG21,A.DG20
  strand#4  U DNA glyco-bond=-s- 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

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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)