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Binding of a Telomestatin Derivative Changes the Mechanical Anisotropy of a Human Telomeric G‐Quadruplex
Author(s) -
Jonchhe Sagun,
Ghimire Chiran,
Cui Yunxi,
Sasaki Shogo,
McCool Mason,
Park Soyoung,
Iida Keisuke,
Nagasawa Kazuo,
Sugiyama Hiroshi,
Mao Hanbin
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201811046
Subject(s) - g quadruplex , ligand (biochemistry) , tetrad , biomolecule , chemistry , stacking , mechanochemistry , anisotropy , molecule , biophysics , dna , physics , biochemistry , biology , receptor , organic chemistry , quantum mechanics , mathematical physics
Abstract Mechanical anisotropy is an essential property for biomolecules to assume structural and functional roles in mechanobiology. However, there is insufficient information on the mechanical anisotropy of ligand–biomolecule complexes. Herein, we investigated the mechanical property of individual human telomeric G‐quadruplexes bound to telomestatin, using optical tweezers. Stacking of the ligand to the G‐tetrad planes changes the conformation of the G‐quadruplex, which resembles a balloon squeezed in certain directions. Such a squeezed balloon effect strengthens the G‐tetrad planes, but dislocates and weakens the loops in the G‐quadruplex upon ligand binding. These dynamic interactions indicate that the binding between the ligand and G‐quadruplex follows the induced‐fit model. We anticipate that the altered mechanical anisotropy of the ligand–G‐quadruplex complex can add additional level of regulations on the motor enzymes that process DNA or RNA molecules.