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...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4550381?pdf=render |
| _version_ | 1828344460280332288 |
|---|---|
| author | Yanan Guo Tino Wolter Tomáš Kubař Martin Sumser Dirk Trauner Marcus Elstner |
| author_facet | Yanan Guo Tino Wolter Tomáš Kubař Martin Sumser Dirk Trauner Marcus Elstner |
| author_sort | Yanan Guo |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-13T23:57:54Z |
| format | Article |
| id | doaj.art-d0249d15ab0845d7aaf69e47d2b3ae40 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T23:57:54Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-d0249d15ab0845d7aaf69e47d2b3ae402022-12-22T02:23:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01108e013539910.1371/journal.pone.0135399Molecular Dynamics Investigation of gluazo, a Photo-Switchable Ligand for the Glutamate Receptor GluK2.Yanan GuoTino WolterTomáš KubařMartin SumserDirk TraunerMarcus ElstnerPhotochromic 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.http://europepmc.org/articles/PMC4550381?pdf=render |
| spellingShingle | Yanan Guo Tino Wolter Tomáš Kubař Martin Sumser Dirk Trauner Marcus Elstner Molecular Dynamics Investigation of gluazo, a Photo-Switchable Ligand for the Glutamate Receptor GluK2. PLoS ONE |
| 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 |
| url | http://europepmc.org/articles/PMC4550381?pdf=render |
| work_keys_str_mv | AT yananguo moleculardynamicsinvestigationofgluazoaphotoswitchableligandfortheglutamatereceptorgluk2 AT tinowolter moleculardynamicsinvestigationofgluazoaphotoswitchableligandfortheglutamatereceptorgluk2 AT tomaskubar moleculardynamicsinvestigationofgluazoaphotoswitchableligandfortheglutamatereceptorgluk2 AT martinsumser moleculardynamicsinvestigationofgluazoaphotoswitchableligandfortheglutamatereceptorgluk2 AT dirktrauner moleculardynamicsinvestigationofgluazoaphotoswitchableligandfortheglutamatereceptorgluk2 AT marcuselstner moleculardynamicsinvestigationofgluazoaphotoswitchableligandfortheglutamatereceptorgluk2 |