Insights into the binding of Phenyltiocarbamide (PTC) agonist to its target human TAS2R38 bitter receptor.

Humans' bitter taste perception is mediated by the hTAS2R subfamily of the G protein-coupled membrane receptors (GPCRs). Structural information on these receptors is currently limited. Here we identify residues involved in the binding of phenylthiocarbamide (PTC) and in receptor activation in o...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Xevi Biarnés, Alessandro Marchiori, Alejandro Giorgetti, Carmela Lanzara, Paolo Gasparini, Paolo Carloni, Stephan Born, Anne Brockhoff, Maik Behrens, Wolfgang Meyerhof
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7c539980badb433aa3fb2d36290a2b4b
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:7c539980badb433aa3fb2d36290a2b4b
record_format	dspace
spelling	oai:doaj.org-article:7c539980badb433aa3fb2d36290a2b4b2021-11-18T06:35:44ZInsights into the binding of Phenyltiocarbamide (PTC) agonist to its target human TAS2R38 bitter receptor.1932-620310.1371/journal.pone.0012394https://doaj.org/article/7c539980badb433aa3fb2d36290a2b4b2010-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20811630/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Humans' bitter taste perception is mediated by the hTAS2R subfamily of the G protein-coupled membrane receptors (GPCRs). Structural information on these receptors is currently limited. Here we identify residues involved in the binding of phenylthiocarbamide (PTC) and in receptor activation in one of the most widely studied hTAS2Rs (hTAS2R38) by means of structural bioinformatics and molecular docking. The predictions are validated by site-directed mutagenesis experiments that involve specific residues located in the putative binding site and trans-membrane (TM) helices 6 and 7 putatively involved in receptor activation. Based on our measurements, we suggest that (i) residue N103 participates actively in PTC binding, in line with previous computational studies. (ii) W99, M100 and S259 contribute to define the size and shape of the binding cavity. (iii) W99 and M100, along with F255 and V296, play a key role for receptor activation, providing insights on bitter taste receptor activation not emerging from the previously reported computational models.Xevi BiarnésAlessandro MarchioriAlejandro GiorgettiCarmela LanzaraPaolo GaspariniPaolo CarloniStephan BornAnne BrockhoffMaik BehrensWolfgang MeyerhofPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 8, p e12394 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xevi Biarnés Alessandro Marchiori Alejandro Giorgetti Carmela Lanzara Paolo Gasparini Paolo Carloni Stephan Born Anne Brockhoff Maik Behrens Wolfgang Meyerhof Insights into the binding of Phenyltiocarbamide (PTC) agonist to its target human TAS2R38 bitter receptor.
description	Humans' bitter taste perception is mediated by the hTAS2R subfamily of the G protein-coupled membrane receptors (GPCRs). Structural information on these receptors is currently limited. Here we identify residues involved in the binding of phenylthiocarbamide (PTC) and in receptor activation in one of the most widely studied hTAS2Rs (hTAS2R38) by means of structural bioinformatics and molecular docking. The predictions are validated by site-directed mutagenesis experiments that involve specific residues located in the putative binding site and trans-membrane (TM) helices 6 and 7 putatively involved in receptor activation. Based on our measurements, we suggest that (i) residue N103 participates actively in PTC binding, in line with previous computational studies. (ii) W99, M100 and S259 contribute to define the size and shape of the binding cavity. (iii) W99 and M100, along with F255 and V296, play a key role for receptor activation, providing insights on bitter taste receptor activation not emerging from the previously reported computational models.
format	article
author	Xevi Biarnés Alessandro Marchiori Alejandro Giorgetti Carmela Lanzara Paolo Gasparini Paolo Carloni Stephan Born Anne Brockhoff Maik Behrens Wolfgang Meyerhof
author_facet	Xevi Biarnés Alessandro Marchiori Alejandro Giorgetti Carmela Lanzara Paolo Gasparini Paolo Carloni Stephan Born Anne Brockhoff Maik Behrens Wolfgang Meyerhof
author_sort	Xevi Biarnés
title	Insights into the binding of Phenyltiocarbamide (PTC) agonist to its target human TAS2R38 bitter receptor.
title_short	Insights into the binding of Phenyltiocarbamide (PTC) agonist to its target human TAS2R38 bitter receptor.
title_full	Insights into the binding of Phenyltiocarbamide (PTC) agonist to its target human TAS2R38 bitter receptor.
title_fullStr	Insights into the binding of Phenyltiocarbamide (PTC) agonist to its target human TAS2R38 bitter receptor.
title_full_unstemmed	Insights into the binding of Phenyltiocarbamide (PTC) agonist to its target human TAS2R38 bitter receptor.
title_sort	insights into the binding of phenyltiocarbamide (ptc) agonist to its target human tas2r38 bitter receptor.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/7c539980badb433aa3fb2d36290a2b4b
work_keys_str_mv	AT xevibiarnes insightsintothebindingofphenyltiocarbamideptcagonisttoitstargethumantas2r38bitterreceptor AT alessandromarchiori insightsintothebindingofphenyltiocarbamideptcagonisttoitstargethumantas2r38bitterreceptor AT alejandrogiorgetti insightsintothebindingofphenyltiocarbamideptcagonisttoitstargethumantas2r38bitterreceptor AT carmelalanzara insightsintothebindingofphenyltiocarbamideptcagonisttoitstargethumantas2r38bitterreceptor AT paologasparini insightsintothebindingofphenyltiocarbamideptcagonisttoitstargethumantas2r38bitterreceptor AT paolocarloni insightsintothebindingofphenyltiocarbamideptcagonisttoitstargethumantas2r38bitterreceptor AT stephanborn insightsintothebindingofphenyltiocarbamideptcagonisttoitstargethumantas2r38bitterreceptor AT annebrockhoff insightsintothebindingofphenyltiocarbamideptcagonisttoitstargethumantas2r38bitterreceptor AT maikbehrens insightsintothebindingofphenyltiocarbamideptcagonisttoitstargethumantas2r38bitterreceptor AT wolfgangmeyerhof insightsintothebindingofphenyltiocarbamideptcagonisttoitstargethumantas2r38bitterreceptor
_version_	1718424423699054592

Insights into the binding of Phenyltiocarbamide (PTC) agonist to its target human TAS2R38 bitter receptor.

Ejemplares similares