6SX3

Intercalation of heterocyclic ligand between quartets in G-rich tetrahelical structure

6SX3 の概要

• エントリーDOI: 10.2210/pdb6sx3/pdb
• NMR情報: BMRB: 34435
• 分子名称: VK2, ~{N}2,~{N}6-bis(1-methylquinolin-1-ium-3-yl)pyridine-2,6-dicarboxamide (2 entities in total)
• 機能のキーワード: intercalation agcga-quadruplex g-quadruplex heterocyclic ligand, 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: 10337.84

構造登録者

Kotar, A.,Kocman, V.,Plavec, J. (登録日: 2019-09-24, 公開日: 2019-12-11, 最終更新日: 2024-05-15)

主引用文献

Kotar, A.,Kocman, V.,Plavec, J.
Intercalation of a Heterocyclic Ligand between Quartets in a G-Rich Tetrahelical Structure.
Chemistry, 26:814-817, 2020

PubMed Abstract: YES G-rich oligonucleotide VK2 folds into an AGCGA-quadruplex tetrahelical structure distinct and significantly different from G-quadruplexes, even though it contains four G tracts. Herein, a bis-quinolinium ligand 360A with high affinity for G-quadruplex structures and selective telomerase inhibition is shown to strongly bind to VK2. Upon binding, 360A does not induce a conformational switch from VK2 to an expected G-quadruplex. In contrast, NMR structural study revealed formation of a well-defined VK2-360A complex with a 1:1 binding stoichiometry, in which 360A intercalates between GAGA- and GCGC-quartets in the central cavity of VK2. This is the first high-resolution structure of a G-quadruplex ligand intercalating into a G-rich tetrahelical fold. This unique mode of ligand binding into tetrahelical DNA architecture offers insights into the stabilization of an AGCGA-quadruplex by a heterocyclic ligand and provides guidelines for rational design of novel VK2 binding molecules with selectivity for different DNA secondary structures.

PubMed: 31750579
DOI: 10.1002/chem.201904923

実験手法

SOLUTION NMR