Summary information

PDB id
7v3t
Class
DNA
Method
NMR
Summary
Solution structure of thrombin binding aptamer g-quadruplex bound a self-adaptive small molecule with rotated ligands
Reference
Zhu BC, He J, Xia XY, Jiang J, Liu W, Liu LY, Liang BB, Yao HG, Ke Z, Xia W, Mao ZW (2022): "Solution structure of a thrombin binding aptamer complex with a non-planar platinum(ii) compound." Chem Sci, 13, 8371-8379. doi: 10.1039/d2sc01196d.
Abstract
Thrombin Binding Aptamer (TBA) is a monomolecular well-defined two G-tetrad antiparallel G-quadruplex DNA that inhibits the activity of human α-thrombin. In this report, we synthesized a quasi-cross-shaped platinum(ii) compound (L'2LPt) with one cyclometalated and two carbene ligands. We found L'2LPt has selective affinity to bind the TBA G-quadruplex. A fibrinogen clotting assay revealed that L'2LPt can abrogate the inhibitory activity of TBA against thrombin. We solved the 1 : 1 L'2LPt-TBA complex structure by NMR, which revealed a unique self-adaptive property of L'2LPt upon binding to TBA. In the complex, a carbene ligand of L'2LPt rotates to pair with the cyclometalated ligand to form a plane stacking over half of the TBA G-tetrad and covered by lateral TT loops. It is notable that the heavy atom Pt stays out of the G-tetrad. Meanwhile, the other carbene ligand remains relatively perpendicular and forms a hydrogen bond with a guanine to anchor the L'2LPt position. This structure exhibits a quasi-cross-shaped Pt(ii) compound bound to the G-quadruplex with an unusual "wall-mounted" binding mode. Our structures provide insights into the specific recognition of antiparallel G-quadruplex DNA by a self-adaptive Pt(ii) compound and useful information for the design of selective G-quadruplex targeting non-planar molecules.
G4 notes
2 G-tetrads, 1 G4 helix, 1 G4 stem, 2(+Ln+Lw+Ln), chair(2+2), UDUD

Base-block schematics in six views

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List of 2 G-tetrads

 1 glyco-bond=s-s- sugar=.... groove=wnwn planarity=0.207 type=other  nts=4 GGGG A.DG1,A.DG15,A.DG10,A.DG6
 2 glyco-bond=-s-s sugar=..3- groove=wnwn planarity=0.232 type=other  nts=4 GGGG A.DG2,A.DG14,A.DG11,A.DG5

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, 2 G-tetrad layers, INTRA-molecular, with 1 stem

 1  glyco-bond=s-s- sugar=.... groove=wnwn Major-->WC nts=4 GGGG A.DG1,A.DG15,A.DG10,A.DG6
 2  glyco-bond=-s-s sugar=..3- groove=wnwn WC-->Major nts=4 GGGG A.DG2,A.DG14,A.DG11,A.DG5
  step#1  mm(<>,outward)  area=13.11 rise=4.02 twist=17.0
  strand#1 DNA glyco-bond=s- sugar=.. nts=2 GG A.DG1,A.DG2
  strand#2 DNA glyco-bond=-s sugar=.. nts=2 GG A.DG15,A.DG14
  strand#3 DNA glyco-bond=s- sugar=.3 nts=2 GG A.DG10,A.DG11
  strand#4 DNA glyco-bond=-s sugar=.- nts=2 GG A.DG6,A.DG5

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1 stacking diagram 
 1  glyco-bond=s-s- sugar=.... groove=wnwn Major-->WC nts=4 GGGG A.DG1,A.DG15,A.DG10,A.DG6
 2  glyco-bond=-s-s sugar=..3- groove=wnwn WC-->Major nts=4 GGGG A.DG2,A.DG14,A.DG11,A.DG5
  step#1  mm(<>,outward)  area=13.11 rise=4.02 twist=17.0

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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, 2 G-tetrad layers, 3 loops, INTRA-molecular, UDUD, anti-parallel, 2(+Ln+Lw+Ln), chair(2+2)

 1  glyco-bond=s-s- sugar=.... groove=wnwn Major-->WC nts=4 GGGG A.DG1,A.DG15,A.DG10,A.DG6
 2  glyco-bond=-s-s sugar=..3- groove=wnwn WC-->Major nts=4 GGGG A.DG2,A.DG14,A.DG11,A.DG5
  step#1  mm(<>,outward)  area=13.11 rise=4.02 twist=17.0
  strand#1  U DNA glyco-bond=s- sugar=.. nts=2 GG A.DG1,A.DG2
  strand#2  D DNA glyco-bond=-s sugar=.. nts=2 GG A.DG15,A.DG14
  strand#3  U DNA glyco-bond=s- sugar=.3 nts=2 GG A.DG10,A.DG11
  strand#4  D DNA glyco-bond=-s sugar=.- nts=2 GG A.DG6,A.DG5
  loop#1 type=lateral   strands=[#1,#4] nts=2 TT A.DT3,A.DT4
  loop#2 type=lateral   strands=[#4,#3] nts=3 TGT A.DT7,A.DG8,A.DT9
  loop#3 type=lateral   strands=[#3,#2] nts=2 TT A.DT12,A.DT13

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