6ZL9

Structure of a parallel c-Myc modified with 5' duplex stem-loop overhang

6ZL9 の概要

• エントリーDOI: 10.2210/pdb6zl9/pdb
• NMR情報: BMRB: 34525
• 分子名称: DNA (35-MER) (1 entity in total)
• 機能のキーワード: g-quadruplex, duplex, quadruplex-duplex junction, dna
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 10986.03

構造登録者

Vianney, Y.M.,Weisz, K. (登録日: 2020-06-30, 公開日: 2020-10-07, 最終更新日: 2024-06-19)

主引用文献

Vianney, Y.M.,Preckwinkel, P.,Mohr, S.,Weisz, K.
Quadruplex-Duplex Junction: A High-Affinity Binding Site for Indoloquinoline Ligands.
Chemistry, 26:16910-16922, 2020

PubMed Abstract: A parallel quadruplex derived from the Myc promoter sequence was extended by a stem-loop duplex at either its 5'- or 3'-terminus to mimic a quadruplex-duplex (Q-D) junction as a potential genomic target. High-resolution structures of the hybrids demonstrate continuous stacking of the duplex on the quadruplex core without significant perturbations. An indoloquinoline ligand carrying an aminoalkyl side chain was shown to bind the Q-D hybrids with a very high affinity in the order K ≈10  m irrespective of the duplex location at the quadruplex 3'- or 5'-end. NMR chemical shift perturbations identified the tetrad face of the Q-D junction as specific binding site for the ligand. However, calorimetric analyses revealed significant differences in the thermodynamic profiles upon binding to hybrids with either a duplex extension at the quadruplex 3'- or 5'-terminus. A large enthalpic gain and considerable hydrophobic effects are accompanied by the binding of one ligand to the 3'-Q-D junction, whereas non-hydrophobic entropic contributions favor binding with formation of a 2:1 ligand-quadruplex complex in case of the 5'-Q-D hybrid.

PubMed: 32975874
DOI: 10.1002/chem.202003540

実験手法

SOLUTION NMR