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dc.creatorArias, Hugo Rubén-
dc.creatorFeuerbach, Dominik-
dc.creatorOrtells, Marcelo Oscar-
dc.date2018-03-08T19:52:38Z-
dc.date2018-03-08T19:52:38Z-
dc.date2015-07-
dc.date2018-03-08T19:02:27Z-
dc.date.accessioned2019-04-29T15:29:34Z-
dc.date.available2019-04-29T15:29:34Z-
dc.date.issued2018-03-08T19:52:38Z-
dc.date.issued2018-03-08T19:52:38Z-
dc.date.issued2015-07-
dc.date.issued2018-03-08T19:02:27Z-
dc.identifierArias, Hugo Rubén; Feuerbach, Dominik; Ortells, Marcelo Oscar; Functional and structural interaction of (-)-lobeline with human α4β2 and α4β4 nicotinic acetylcholine receptor subtypes; Pergamon-Elsevier Science Ltd; International Journal Of Biochemistry And Cellular Biology; 64; 7-2015; 15-24-
dc.identifier1357-2725-
dc.identifierhttp://hdl.handle.net/11336/38315-
dc.identifierCONICET Digital-
dc.identifierCONICET-
dc.identifier.urihttp://rodna.bn.gov.ar:8080/jspui/handle/bnmm/295130-
dc.descriptionTo determine the pharmacologic activity of (-)-lobeline between human (h)α4β2 and hα4β4 nicotinic acetylcholine receptors (AChRs), functional and structural experiments were performed. The Ca2+ influx results established that (-)-lobeline neither actives nor enhances the function of the studied AChR subtypes, but competitively inhibits hα4β4 AChRs with potency ∼10-fold higher than that for hα4β2 AChRs. This difference is due to a higher binding affinity for the [3H]cytisine sites at hα4β4 compared to hα4β2 AChRs, which, in turn, can be explained by our molecular dynamics (MD) results: (1) higher stability of (-)-lobeline and its hydrogen bonds within the α4β4 pocket compared to the α4β2 pocket, (2) (-)-lobeline promotes Loop C to cap the binding site at the α4β4 pocket, but forces Loop C to get apart from the α4β2 pocket, precluding the gating process elicited by agonists, and (3) the orientation of (-)-lobeline within the α4β4, but not the α4β2, subpocket, promoted by the t-(or t+) rotameric state of α4-Tyr98, remains unchanged during the whole MD simulation. This study gives a detailed view of the molecular and dynamics events evoked by (-)-lobeline supporting the differential binding affinity and subsequent inhibitory potency between hα4β2 and hα4β4 AChRs, and supports the possibility that the latter subtype is also involved in its activity.-
dc.descriptionFil: Arias, Hugo Rubén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. California Northstate University. College of Medicine. Department of Medical Education; Estados Unidos-
dc.descriptionFil: Feuerbach, Dominik. Novartis Institutes for Biomedical Research. Neuroscience Research; Suiza-
dc.descriptionFil: Ortells, Marcelo Oscar. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Morón; Argentina-
dc.formatapplication/pdf-
dc.formatapplication/pdf-
dc.languageeng-
dc.publisherPergamon-Elsevier Science Ltd-
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.biocel.2015.03.003-
dc.relationinfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1357272515000722-
dc.rightsinfo:eu-repo/semantics/restrictedAccess-
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/-
dc.sourcereponame:CONICET Digital (CONICET)-
dc.sourceinstname:Consejo Nacional de Investigaciones Científicas y Técnicas-
dc.sourceinstacron:CONICET-
dc.subject(-)-LOBELINE-
dc.subjectACETYLCHOLINE RECEPTORS-
dc.subjectCA<SUP>2+</SUP>INFLUX-
dc.subjectCOMPETITIVE ANTAGONIST-
dc.subjectHUMAN Α4 Β2 AND Α4 Β4 NICOTINIC-
dc.subjectMOLECULAR MODELING-
dc.subjectOtras Ciencias Biológicas-
dc.subjectCiencias Biológicas-
dc.subjectCIENCIAS NATURALES Y EXACTAS-
dc.titleFunctional and structural interaction of (-)-lobeline with human α4β2 and α4β4 nicotinic acetylcholine receptor subtypes-
dc.typeinfo:eu-repo/semantics/article-
dc.typeinfo:eu-repo/semantics/publishedVersion-
dc.typeinfo:ar-repo/semantics/articulo-
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