2L7V

Quindoline/G-quadruplex complex

2L7V の概要

• エントリーDOI: 10.2210/pdb2l7v/pdb
• NMR情報: BMRB: 17379
• 分子名称: DNA (5'-D(*TP*GP*AP*GP*GP*GP*TP*GP*GP*GP*TP*AP*GP*GP*GP*TP*GP*GP*GP*TP*AP*A)-3'), POTASSIUM ION, N,N-diethyl-N'-(10H-indolo[3,2-b]quinolin-11-yl)ethane-1,2-diamine (3 entities in total)
• 機能のキーワード: c-myc promoter, dna-inhibitor complex, c-myc promoter g-quadruplex, dna/inhibitor
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 7751.59

構造登録者

Dai, J.,Carver, M.,Mathad, R.,Yang, D. (登録日: 2010-12-23, 公開日: 2011-11-09, 最終更新日: 2024-05-01)

主引用文献

Dai, J.,Carver, M.,Hurley, L.H.,Yang, D.
Solution Structure of a 2:1 Quindoline-c-MYC G-Quadruplex: Insights into G-Quadruplex-Interactive Small Molecule Drug Design.
J.Am.Chem.Soc., 133:17673-17680, 2011

PubMed Abstract: Unimolecular parallel-stranded G-quadruplex structures are found to be prevalent in gene promoters. The nuclease hypersensitivity element III(1) (NHE III(1)) of the c-MYC promoter can form transcriptionally active and silenced forms, and the formation of DNA G-quadruplex structures has been shown to be critical for c-MYC transcriptional silencing. The solution structure of a 2:1 quindoline-G-quadruplex complex has been solved and shows unexpected features, including the drug-induced reorientation of the flanking sequences to form a new binding pocket. While both 3' and 5' complexes show overall similar features, there are identifiable differences that emphasize the importance of both stacking and electronic interactions. For the first time, we describe the importance of the shape of the ligand as well as the two flanking bases in determining drug binding specificity. These structures provide important insights for the structure-based rational design of drugs that bind to unimolecular parallel G-quadruplexes commonly found in promoter elements.

PubMed: 21967482
DOI: 10.1021/ja205646q

実験手法

SOLUTION NMR