7V3T

Solution structure of thrombin binding aptamer G-quadruplex bound a self-adaptive small molecule with rotated ligands

Summary for 7V3T

• Entry DOI: 10.2210/pdb7v3t/pdb
• Descriptor: TBA G4 DNA (5'-D(*GP*GP*TP*TP*GP*GP*TP*GP*TP*GP*GP*TP*TP*GP*G)-3'), 11,13-bis(fluoranyl)-8-(1-methyl-3-pyridin-2-yl-imidazol-2-yl)-8-(1-methyl-3-pyridin-2-yl-imidazol-2-yl)-7$l^{4}-aza-8$l^{4}-platinatricyclo[7.4.0.0^{2,7}]trideca-1(9),2(7),3,5,10,12-hexaene (2 entities in total)
• Functional Keywords: g-quadruplex, platinum compound, thrombin binding aptamer, dna-ligand complex structure, dna
• Biological source: Homo sapiens
• Total number of polymer chains: 1
• Total formula weight: 5446.67

Authors

Liu, W.,Zhu, B.C.,Mao, Z.W. (deposition date: 2021-08-11, release date: 2022-09-28, Last modification date: 2024-05-15)

Primary citation

Zhu, B.C.,He, J.,Xia, X.Y.,Jiang, J.,Liu, W.,Liu, L.Y.,Liang, B.B.,Yao, H.G.,Ke, Z.,Xia, W.,Mao, Z.W.
Solution structure of a thrombin binding aptamer complex with a non-planar platinum(ii) compound.
Chem Sci, 13:8371-8379, 2022

PubMed 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'LPt) with one cyclometalated and two carbene ligands. We found L'LPt has selective affinity to bind the TBA G-quadruplex. A fibrinogen clotting assay revealed that L'LPt can abrogate the inhibitory activity of TBA against thrombin. We solved the 1 : 1 L'LPt-TBA complex structure by NMR, which revealed a unique self-adaptive property of L'LPt upon binding to TBA. In the complex, a carbene ligand of L'LPt 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'LPt 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.

PubMed: 35919711
DOI: 10.1039/d2sc01196d

Experimental method

SOLUTION NMR