Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/9764
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dc.contributor.authorRezmann-Vitti, Linda Aen
dc.contributor.authorLouis, Simon N Sen
dc.contributor.authorNero, Tracy Len
dc.contributor.authorJackman, Graham Pen
dc.contributor.authorMachida, Curtis Aen
dc.contributor.authorLouis, William Jen
dc.date.accessioned2015-05-15T22:58:35Z
dc.date.available2015-05-15T22:58:35Z
dc.date.issued2004-07-01en
dc.identifier.citationEuropean Journal of Medicinal Chemistry; 39(7): 625-31en
dc.identifier.govdoc15236843en
dc.identifier.otherPUBMEDen
dc.identifier.urihttp://ahro.austin.org.au/austinjspui/handle/1/9764en
dc.description.abstractTo determine the role played by Tyr(356 (7.43)) in the rat beta(1)-adrenoceptor in binding the antagonists (+/-)cyanopindolol (4-[3-(t-butylamino]-3-(2'-cyano-indoloxy)-2-propanolol) and its iodinated analogue (+/-)[(125)Iodo]cyanopindolol (1-(t-butylamino]-3-(2'-cyano-3'-iodo-indoloxy)-2-propanolol), Tyr(356 (7.43)) was mutated to either Phe or Ala and binding affinities determined for wild type and mutant rat beta(1)-adrenoceptors. Our results indicate that Tyr(356 (7.43)) is important for (+/-)cyanopindolol, but not (+/-)[(125)Iodo]cyanopindolol, binding and that (+/-)cyanopindolol adopts a "reverse" binding orientation whereas (+/-)[(125)Iodo]cyanopindolol cannot be accommodated in this binding mode. We define a "reverse" antagonist binding mode as one where the aryloxy moiety interacts with residues on transmembrane helices 1, 2, 3 and 7. The beta(1)-adrenoceptor site-directed mutagenesis results are the first to support a "reverse" antagonist binding orientation and the involvement of Tyr(356 (7.43)) in this binding mode.en
dc.language.isoenen
dc.subject.otherAdrenergic beta-Antagonists.chemistry.metabolism.pharmacologyen
dc.subject.otherAnimalsen
dc.subject.otherIodine Radioisotopesen
dc.subject.otherModels, Molecularen
dc.subject.otherMutagenesis, Site-Directeden
dc.subject.otherPindolol.analogs & derivatives.chemistry.metabolism.pharmacologyen
dc.subject.otherProtein Bindingen
dc.subject.otherProtein Conformationen
dc.subject.otherRadioligand Assayen
dc.subject.otherRatsen
dc.subject.otherReceptors, Adrenergic, beta-1.genetics.metabolismen
dc.subject.otherTyrosine.chemistry.genetics.metabolismen
dc.titleSite-directed mutagenesis of the rat beta1-adrenoceptor. Involvement of Tyr356 (7.43) in (+/-)cyanopindolol but not (+/-)[125Iodo]cyanopindolol binding.en
dc.typeJournal Articleen
dc.identifier.journaltitleEuropean journal of medicinal chemistryen
dc.identifier.affiliationClinical Pharmacology and Therapeutics Unit, Department of Medicine, The University of Melbourne, Austin Health, Heidelberg, 3084 Victoria, Australiaen
dc.identifier.doi10.1016/j.ejmech.2004.03.009en
dc.description.pages625-31en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/15236843en
dc.type.austinJournal Articleen
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.fulltextNo Fulltext-
item.cerifentitytypePublications-
item.grantfulltextnone-
item.languageiso639-1en-
item.openairetypeJournal Article-
crisitem.author.deptClinical Pharmacology and Therapeutics-
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