6IJV

Solution NMR structure of a 14-mer dsDNA complexed with a novel NIR fluorescent probe QCy-DT

6IJV の概要

• エントリーDOI: 10.2210/pdb6ijv/pdb
• 分子名称: DNA (5'-D(*CP*GP*CP*GP*AP*AP*AP*TP*TP*TP*CP*GP*CP*G)-3'), 2,2'-{(4-hydroxy-1,3-phenylene)di[(E)ethene-2,1-diyl]}bis(3-methyl-1,3-benzothiazol-3-ium) (2 entities in total)
• 機能のキーワード: dsdna, ligand, qcy-dt, dna
• 由来する生物種: Homo sapiens
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 9004.18

構造登録者

Basu, G.,Ganguly, S. (登録日: 2018-10-12, 公開日: 2019-03-06, 最終更新日: 2024-05-15)

主引用文献

Ganguly, S.,Murugan, N.A.,Ghosh, D.,Narayanaswamy, N.,Govindaraju, T.,Basu, G.
DNA Minor Groove-Induced cis - trans Isomerization of a Near-Infrared Fluorescent Probe.
Biochemistry, 2021

PubMed Abstract: The discovery of small molecules that exhibit turn-on far-red or near-infrared (NIR) fluorescence upon DNA binding and understanding how they bind DNA are important for imaging and bioanalytical applications. Here we report the DNA-bound structure and the DNA binding mechanism of quinone cyanine dithiazole (QCy-DT), a recently reported AT-specific turn-on NIR fluorescent probe for double-stranded DNA. The nuclear magnetic resonance (NMR)-derived structure showed minor groove binding but no specific ligand-DNA interactions, consistent with an endothermic and entropy-driven binding mechanism deduced from isothermal titration calorimetry. Minor groove binding is typically fast because it minimally perturbs the DNA structure. However, QCy-DT exhibited unusually slow DNA binding. The cyanine-based probe is capable of - isomerization due to overlapping methine bridges, with 16 possible slowly interconverting / isomers. Using NMR, density functional theory, and free energy calculations, we show that the DNA-free and DNA-bound environments of QCy-DT prefer distinctly different isomers, indicating that the origin of the slow kinetics is a - isomerization and that the minor groove preferentially selects an otherwise unstable / isomer of QCy-DT. Flux analysis showed the conformational selection pathway to be the dominating DNA binding mechanism at low DNA concentrations, which switches to the induced fit pathway at high DNA concentrations. This report of / isomerization of a ligand, upon binding the DNA minor groove, expands the prevailing understanding of unique discriminatory powers of the minor groove and has an important bearing on using polymethine cyanine dyes to probe the kinetics of molecular interactions.

PubMed: 34142803
DOI: 10.1021/acs.biochem.1c00281

実験手法

SOLUTION NMR