3CDM

Structural adaptation and conservation in quadruplex-drug recognition

3CDM の概要

• エントリーDOI: 10.2210/pdb3cdm/pdb
• 関連するPDBエントリー: 3CCO
• 分子名称: DNA (5'-D(*DT*DAP*DGP*DGP*DGP*DTP*DTP*DAP*DGP*DGP*DGP*DTP*DTP*DAP*DGP*DGP*DGP*DTP*DTP*DAP*DGP*DGP*DG)-3'), 2,7-bis[3-(dimethylamino)propyl]-4,9-bis[(3-hydroxypropyl)amino]benzo[lmn][3,8]phenanthroline-1,3,6,8(2H,7H)-tetrone, POTASSIUM ION, ... (4 entities in total)
• 機能のキーワード: quadruplex, dna, propeller, intramolecular, human telomere parallel stranded, ligand, complex
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 18227.92

構造登録者

Parkinson, G.N.,Neidle, S. (登録日: 2008-02-27, 公開日: 2008-09-23, 最終更新日: 2023-11-01)

主引用文献

Parkinson, G.N.,Cuenca, F.,Neidle, S.
Topology conservation and loop flexibility in quadruplex-drug recognition: crystal structures of inter- and intramolecular telomeric DNA quadruplex-drug complexes
J.Mol.Biol., 381:1145-1156, 2008

PubMed Abstract: Knowledge of the biologically relevant topology is critical for the design of drugs targeting quadruplex nucleic acids. We report here crystal structures of a G-quadruplex-selective ligand complexed with two human telomeric DNA quadruplexes. The intramolecular quadruplex sequence d[TAGGG(TTAGGG)(3)] and the bimolecular quadruplex sequence d(TAGGGTTAGGGT) were co-crystallized with a tetra-substituted naphthalene diimide quadruplex-binding ligand. The structures were solved and refined to 2.10- and 2.20-A resolution, respectively, revealing that the quadruplex topology in both structures is unchanged by the addition of the ligands, retaining a parallel-stranded arrangement with external double-chain-reversal propeller loops. The parallel topology results in accessible external 5' and 3' planar G-tetrad surfaces for ligand stacking. This also enables significant ligand-induced conformational changes in several TTA propeller loops to take place such that the loops themselves are able to accommodate bound drug molecules without affecting the parallel quadruplex topology, by stacking on the external TTA connecting loop nucleotides. Ligands are bound into the external TTA loop nucleotides and stack onto G-tetrad surfaces. These crystal structures provide a framework for further ligand development of the naphthalene diimide series to enhance selectivity and affinity.

PubMed: 18619463
DOI: 10.1016/j.jmb.2008.06.022

実験手法

X-RAY DIFFRACTION (2.1 Å)