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Molecular Dynamics Investigation of gluazo, a Photo-Switchable Ligand for the Glutamate Receptor GluK2
Photochromic ligands (PCLs), defined as photoswitchable molecules that are able to endow native receptors with a sensitivity towards light, have become a promising photopharmacological tool for various applications in biology. In general, PCLs consist of a ligand of the target receptor covalently li...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4550381/ https://www.ncbi.nlm.nih.gov/pubmed/26308344 http://dx.doi.org/10.1371/journal.pone.0135399 |
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author | Guo, Yanan Wolter, Tino Kubař, Tomáš Sumser, Martin Trauner, Dirk Elstner, Marcus |
author_facet | Guo, Yanan Wolter, Tino Kubař, Tomáš Sumser, Martin Trauner, Dirk Elstner, Marcus |
author_sort | Guo, Yanan |
collection | PubMed |
description | Photochromic ligands (PCLs), defined as photoswitchable molecules that are able to endow native receptors with a sensitivity towards light, have become a promising photopharmacological tool for various applications in biology. In general, PCLs consist of a ligand of the target receptor covalently linked to an azobenzene, which can be reversibly switched between two configurations upon light illumination. Gluazo, as a PCL that targets excitatory amino acid receptors, in its dark-adapted trans iso-form was characterized to be a partial agonist of the kainate glutamate receptor GluK2. Application of UV light leads to the formation of the cis form, with remarkedly reduced affinity towards GluK2. The mechanism of the change of ligand affinity induced by the photoisomerization was unresolved. The presented computational study explains how the isomerization of such a PCL affects the structural changes in the target receptor that lead to its activation. |
format | Online Article Text |
id | pubmed-4550381 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-45503812015-09-01 Molecular Dynamics Investigation of gluazo, a Photo-Switchable Ligand for the Glutamate Receptor GluK2 Guo, Yanan Wolter, Tino Kubař, Tomáš Sumser, Martin Trauner, Dirk Elstner, Marcus PLoS One Research Article Photochromic ligands (PCLs), defined as photoswitchable molecules that are able to endow native receptors with a sensitivity towards light, have become a promising photopharmacological tool for various applications in biology. In general, PCLs consist of a ligand of the target receptor covalently linked to an azobenzene, which can be reversibly switched between two configurations upon light illumination. Gluazo, as a PCL that targets excitatory amino acid receptors, in its dark-adapted trans iso-form was characterized to be a partial agonist of the kainate glutamate receptor GluK2. Application of UV light leads to the formation of the cis form, with remarkedly reduced affinity towards GluK2. The mechanism of the change of ligand affinity induced by the photoisomerization was unresolved. The presented computational study explains how the isomerization of such a PCL affects the structural changes in the target receptor that lead to its activation. Public Library of Science 2015-08-26 /pmc/articles/PMC4550381/ /pubmed/26308344 http://dx.doi.org/10.1371/journal.pone.0135399 Text en © 2015 Guo et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Guo, Yanan Wolter, Tino Kubař, Tomáš Sumser, Martin Trauner, Dirk Elstner, Marcus Molecular Dynamics Investigation of gluazo, a Photo-Switchable Ligand for the Glutamate Receptor GluK2 |
title | Molecular Dynamics Investigation of gluazo, a Photo-Switchable Ligand for the Glutamate Receptor GluK2 |
title_full | Molecular Dynamics Investigation of gluazo, a Photo-Switchable Ligand for the Glutamate Receptor GluK2 |
title_fullStr | Molecular Dynamics Investigation of gluazo, a Photo-Switchable Ligand for the Glutamate Receptor GluK2 |
title_full_unstemmed | Molecular Dynamics Investigation of gluazo, a Photo-Switchable Ligand for the Glutamate Receptor GluK2 |
title_short | Molecular Dynamics Investigation of gluazo, a Photo-Switchable Ligand for the Glutamate Receptor GluK2 |
title_sort | molecular dynamics investigation of gluazo, a photo-switchable ligand for the glutamate receptor gluk2 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4550381/ https://www.ncbi.nlm.nih.gov/pubmed/26308344 http://dx.doi.org/10.1371/journal.pone.0135399 |
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