rdf:type |
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lifeskim:mentions |
|
pubmed:issue |
5
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pubmed:dateCreated |
1990-5-31
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pubmed:abstractText |
The molecular basis of ligand binding selectivity to beta-adrenergic receptor subtypes was investigated by designing chimeric beta 1/beta 2-adrenergic receptors. These molecules consisted of a set of reciprocal constructions, obtained by the exchange between the wild-type receptor genes of one to three unmodified transmembrane regions, together with their extracellular flanking regions. Eight different chimeras were expressed in Escherichia coli and studied with selective beta-adrenergic ligands. The evaluation of the relative effect of each chimeric exchange on ligand binding affinity was based on the analysis of delta G values, calculated from the equilibrium binding constants, as a function of the number of substituted beta 2-adrenergic receptor transmembrane domains. The data showed that the contribution of each exchanged region to subtype selectivity varies with each ligand; moreover, while several regions are critical for the pharmacological selectivity of all ligands, others are involved in the selectivity of only some compounds. The selectivity displayed by beta-adrenergic compounds towards beta 1 or beta 2 receptor subtypes thus results from a particular combination of interactions between each ligand and each of the subsites, variably distributed over the seven transmembrane regions of the receptor; these subsites are presumably defined by the individual structural properties of the ligands.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/1970295-1161000,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1970295-2431904,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1970295-2474546,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1970295-2536189,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1970295-2542304,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1970295-2580220,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1970295-2821000,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1970295-2823249,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1970295-2825170,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1970295-2828022,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1970295-2831218,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1970295-2836401,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1970295-2837273,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1970295-2840663,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1970295-2841758,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1970295-2845411,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1970295-2846532,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1970295-2849109,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1970295-2881211,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1970295-2885836,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1970295-2890637,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1970295-2899076,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1970295-2948499,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1970295-2985470,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1970295-3010132,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1970295-3025863,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1970295-3027509,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1970295-3128532,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1970295-39246,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1970295-4202581
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pubmed:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/CGP 20712A,
http://linkedlifedata.com/resource/pubmed/chemical/Ethanolamines,
http://linkedlifedata.com/resource/pubmed/chemical/ICI 118551,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Norepinephrine,
http://linkedlifedata.com/resource/pubmed/chemical/Procaterol,
http://linkedlifedata.com/resource/pubmed/chemical/Propanolamines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenergic, beta,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0261-4189
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:volume |
9
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
1471-6
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:1970295-Adrenergic beta-Agonists,
pubmed-meshheading:1970295-Adrenergic beta-Antagonists,
pubmed-meshheading:1970295-Amino Acid Sequence,
pubmed-meshheading:1970295-Animals,
pubmed-meshheading:1970295-Escherichia coli,
pubmed-meshheading:1970295-Ethanolamines,
pubmed-meshheading:1970295-Imidazoles,
pubmed-meshheading:1970295-Kinetics,
pubmed-meshheading:1970295-Molecular Sequence Data,
pubmed-meshheading:1970295-Norepinephrine,
pubmed-meshheading:1970295-Procaterol,
pubmed-meshheading:1970295-Propanolamines,
pubmed-meshheading:1970295-Protein Engineering,
pubmed-meshheading:1970295-Receptors, Adrenergic, beta,
pubmed-meshheading:1970295-Recombinant Fusion Proteins,
pubmed-meshheading:1970295-Structure-Activity Relationship,
pubmed-meshheading:1970295-Thermodynamics
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pubmed:year |
1990
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pubmed:articleTitle |
Selective binding of ligands to beta 1, beta 2 or chimeric beta 1/beta 2-adrenergic receptors involves multiple subsites.
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pubmed:affiliation |
Laboratoire de Biologie Moléculaire des Récepteurs, CNRS, Université Paris VII, Institut Pasteur, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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