Solution structures of a G-quadruplex bound to linear- and cyclic-dinucleotides

Cyclic dinucleotides have emerged as important secondary messengers and cell signaling molecules that regulate several cell responses. A guanine-deficit G-quadruplex structure formation by a sequence containing (4n – 1) guanines, n denoting the number of G-tetrad layers, was previously reported. Her...

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Main Authors: Winnerdy, Fernaldo Richtia, Das, Poulomi, Heddi, Brahim, Phan, Anh Tuân
Other Authors: School of Physical and Mathematical Sciences
Format: Article
Language:English
Published: 2020
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Online Access:https://hdl.handle.net/10356/140171
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spelling sg-ntu-dr.10356-1401712023-02-28T19:46:42Z Solution structures of a G-quadruplex bound to linear- and cyclic-dinucleotides Winnerdy, Fernaldo Richtia Das, Poulomi Heddi, Brahim Phan, Anh Tuân School of Physical and Mathematical Sciences NTU Institute of Structural Biology Science::Chemistry Ligands Genetics Cyclic dinucleotides have emerged as important secondary messengers and cell signaling molecules that regulate several cell responses. A guanine-deficit G-quadruplex structure formation by a sequence containing (4n – 1) guanines, n denoting the number of G-tetrad layers, was previously reported. Here, a (4n – 1) G-quadruplex structure is shown to be capable of binding guanine-containing dinucleotides in micromolar affinity. The guanine base of the dinucleotides interacts with a vacant G-triad, forming four additional Hoogsteen hydrogen bonds to complete a G-tetrad. Solution structures of two complexes, both comprised of a (4n – 1) G-quadruplex structure, one bound to a linear dinucleotide (d(AG)) and the other to a cyclic dinucleotide (cGAMP), are solved using NMR spectroscopy. The latter suggests sufficiently strong interaction between the guanine base of the dinucleotide and the vacant G-triad, which acts as an anchor point of binding. The binding interfaces from the two solution structures provide useful information for specific ligand design. The results also infer that other guanine-containing metabolites of a similar size have the capability of binding G-quadruplexes, potentially affecting the expression of the metabolites and functionality of the bound G-quadruplexes. NRF (Natl Research Foundation, S’pore) Accepted version 2020-05-27T03:56:31Z 2020-05-27T03:56:31Z 2019 Journal Article Winnerdy, F. R., Das, P., Heddi, B., & Phan, A. T. (2019). Solution structures of a G-quadruplex bound to linear- and cyclic-dinucleotides. Journal of the American Chemical Society, 141(45), 18038-18047. doi:10.1021/jacs.9b05642 0002-7863 https://hdl.handle.net/10356/140171 10.1021/jacs.9b05642 31661272 2-s2.0-85074952473 45 141 18038 18047 en NRF-NRFI2017-09 Journal of the American Chemical Society This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of the American Chemical Society, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/jacs.9b05642 application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Chemistry
Ligands
Genetics
spellingShingle Science::Chemistry
Ligands
Genetics
Winnerdy, Fernaldo Richtia
Das, Poulomi
Heddi, Brahim
Phan, Anh Tuân
Solution structures of a G-quadruplex bound to linear- and cyclic-dinucleotides
description Cyclic dinucleotides have emerged as important secondary messengers and cell signaling molecules that regulate several cell responses. A guanine-deficit G-quadruplex structure formation by a sequence containing (4n – 1) guanines, n denoting the number of G-tetrad layers, was previously reported. Here, a (4n – 1) G-quadruplex structure is shown to be capable of binding guanine-containing dinucleotides in micromolar affinity. The guanine base of the dinucleotides interacts with a vacant G-triad, forming four additional Hoogsteen hydrogen bonds to complete a G-tetrad. Solution structures of two complexes, both comprised of a (4n – 1) G-quadruplex structure, one bound to a linear dinucleotide (d(AG)) and the other to a cyclic dinucleotide (cGAMP), are solved using NMR spectroscopy. The latter suggests sufficiently strong interaction between the guanine base of the dinucleotide and the vacant G-triad, which acts as an anchor point of binding. The binding interfaces from the two solution structures provide useful information for specific ligand design. The results also infer that other guanine-containing metabolites of a similar size have the capability of binding G-quadruplexes, potentially affecting the expression of the metabolites and functionality of the bound G-quadruplexes.
author2 School of Physical and Mathematical Sciences
author_facet School of Physical and Mathematical Sciences
Winnerdy, Fernaldo Richtia
Das, Poulomi
Heddi, Brahim
Phan, Anh Tuân
format Article
author Winnerdy, Fernaldo Richtia
Das, Poulomi
Heddi, Brahim
Phan, Anh Tuân
author_sort Winnerdy, Fernaldo Richtia
title Solution structures of a G-quadruplex bound to linear- and cyclic-dinucleotides
title_short Solution structures of a G-quadruplex bound to linear- and cyclic-dinucleotides
title_full Solution structures of a G-quadruplex bound to linear- and cyclic-dinucleotides
title_fullStr Solution structures of a G-quadruplex bound to linear- and cyclic-dinucleotides
title_full_unstemmed Solution structures of a G-quadruplex bound to linear- and cyclic-dinucleotides
title_sort solution structures of a g-quadruplex bound to linear- and cyclic-dinucleotides
publishDate 2020
url https://hdl.handle.net/10356/140171
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