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3CCO

Structural adaptation and conservation in quadruplex-drug recognition

3CCO の概要
エントリーDOI10.2210/pdb3cco/pdb
関連するPDBエントリー3CDM
分子名称DNA (5'-D(*DTP*DAP*DGP*DGP*DGP*DTP*DTP*DAP*DGP*DGP*DGP*DT)-3'), SODIUM ION, POTASSIUM ION, ... (5 entities in total)
機能のキーワードquadruplex, dna, propeller, dimeric, human telomere parallel stranded, ligand, complex, naphthalene diimidine
タンパク質・核酸の鎖数1
化学式量合計5661.82
構造登録者
Parkinson, G.N.,Neidle, S. (登録日: 2008-02-26, 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
Cited by
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
主引用文献が同じPDBエントリー
実験手法
X-RAY DIFFRACTION (2.2 Å)
構造検証レポート
Validation report summary of 3cco
検証レポート(詳細版)ダウンロードをダウンロード

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件を2024-10-30に公開中

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