7N7E

Solution structure of the MYC promoter G-quadruplex in complex with berberine: conformer B

7N7E の概要

• エントリーDOI: 10.2210/pdb7n7e/pdb
• 関連するPDBエントリー: 7N7D
• NMR情報: BMRB: 30924
• 分子名称: Myc2345, BERBERINE (2 entities in total)
• 機能のキーワード: g-quadruplex dna, drug-dna complex, berberine, cancer, dna
• 由来する生物種: Homo sapiens
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 7706.24

構造登録者

Dickerhoff, J.,Yang, D. (登録日: 2021-06-10, 公開日: 2021-11-03, 最終更新日: 2024-05-15)

主引用文献

Dickerhoff, J.,Brundridge, N.,McLuckey, S.A.,Yang, D.
Berberine Molecular Recognition of the Parallel MYC G-Quadruplex in Solution.
J.Med.Chem., 64:16205-16212, 2021

PubMed Abstract: The medicinal natural product berberine is one of the most actively studied and pursued G-quadruplex (G4)-ligands. The major G-quadruplex formed in the promoter region of the MYC oncogene (MycG4) is an attractive drug target and a prominent example and model structure for parallel G-quadruplexes. G4-targeted berberine derivatives have been actively developed; however, the analogue design was based on a previous crystal structure in which berberine binds as a dimer to a parallel G-quadruplex. Herein, we show that in solution, the binding mode and stoichiometry of berberine are substantially different from the crystal structure: berberine binds as a monomer to MycG4 using a base-recruitment mechanism with a reversed orientation in that the positively charged convex side is actually positioned above the tetrad center. Our structure provides a physiologically relevant basis for the future structure-based rational design of G4-targeted berberine derivatives, and this study demonstrates that it is crucial to validate the ligand-DNA interactions.

PubMed: 34677968
DOI: 10.1021/acs.jmedchem.1c01508

実験手法

SOLUTION NMR