Hauptseite > Publikationsdatenbank > The importance of valine 114 in ligand binding in beta(2)-adrenergic receptor > print

001     8401
005     20240610120627.0
024 7 _ |2 pmid
|a pmid:19916165
024 7 _ |2 pmc
|a pmc:PMC2817842
024 7 _ |2 DOI
|a 10.1002/pro.285
024 7 _ |2 WOS
|a WOS:000273638700010
037 _ _ |a PreJuSER-8401
041 _ _ |a eng
082 _ _ |a 610
084 _ _ |2 WoS
|a Biochemistry & Molecular Biology
100 1 _ |0 P:(DE-HGF)0
|a Arakawa, M.
|b 0
245 _ _ |a The importance of valine 114 in ligand binding in beta(2)-adrenergic receptor
260 _ _ |a Hoboken, NJ
|b Wiley
|c 2010
300 _ _ |a 85 - 93
336 7 _ |a Journal Article
|0 PUB:(DE-HGF)16
|2 PUB:(DE-HGF)
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|0 0
|2 EndNote
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a article
|2 DRIVER
440 _ 0 |0 10881
|a Protein Science
|v 19
|x 0961-8368
|y 1
500 _ _ |a Grant sponsor: Manitoba Medical Service Foundation (MMSF); Grant sponsor: Canadian Institute of Health Research; Grant number: ROP 92389; Grant sponsor: Manitoba Health Research Council (MHRC); Grant sponsor: National Institutes of Health; Grant number: NIH-NLM 2RO1LM007994-05; Grant sponsor: National Science Foundation; Grant number: CAREER NSF-CC0449117; Grant sponsor: New Investigator Personnel Award from the Heart and Stroke Foundation of Canada (HSFC).
520 _ _ |a G-protein coupled receptors (GPCRs) are transmembrane signaling molecules, with a majority of them performing important physiological roles. beta(2)-Adrenergic receptor (beta(2)-AR) is a well-studied GPCRs that mediates natural responses to the hormones adrenaline and noradrenaline. Analysis of the ligand-binding region of beta(2)-AR using the recently solved high-resolution crystal structures revealed a number of highly conserved amino acids that might be involved in ligand binding. However, detailed structure-function studies on some of these residues have not been performed, and their role in ligand binding remains to be elucidated. In this study, we have investigated the structural and functional role of a highly conserved residue valine 114, in hamster beta(2)-AR by site-directed mutagenesis. We replaced V114 in hamster beta(2)-AR with a number of amino acid residues carrying different functional groups. In addition to the complementary substitutions V114I and V114L, the V114C and V114E mutants also showed significant ligand binding and agonist dependent G-protein activation. However, the V114G, V114T, V114S, and V114W mutants failed to bind ligand in a specific manner. Molecular modeling studies were conducted to interpret these results in structural terms. We propose that the replacement of V114 influences not only the interaction of the ethanolamine side-chains but also the aryl-ring of the ligands tested. Results from this study show that the size and orientation of the hydrophobic residue at position V114 in beta(2)-AR affect binding of both agonists and antagonists, but it does not influence the receptor expression or folding.
536 _ _ |0 G:(DE-Juel1)FUEK443
|2 G:(DE-HGF)
|a Programm Biosoft
|c N03
|x 0
588 _ _ |a Dataset connected to Web of Science, Pubmed
650 _ 2 |2 MeSH
|a Adenylate Cyclase: metabolism
650 _ 2 |2 MeSH
|a Adrenergic beta-Antagonists: pharmacology
650 _ 2 |2 MeSH
|a Alprenolol: pharmacology
650 _ 2 |2 MeSH
|a Animals
650 _ 2 |2 MeSH
|a Binding Sites
650 _ 2 |2 MeSH
|a COS Cells
650 _ 2 |2 MeSH
|a Cercopithecus aethiops
650 _ 2 |2 MeSH
|a Cricetinae
650 _ 2 |2 MeSH
|a Cyclic AMP: metabolism
650 _ 2 |2 MeSH
|a Models, Molecular
650 _ 2 |2 MeSH
|a Mutagenesis, Site-Directed
650 _ 2 |2 MeSH
|a Protein Binding: drug effects
650 _ 2 |2 MeSH
|a Receptors, Adrenergic, beta-2: chemistry
650 _ 2 |2 MeSH
|a Receptors, Adrenergic, beta-2: genetics
650 _ 2 |2 MeSH
|a Receptors, Adrenergic, beta-2: metabolism
650 _ 2 |2 MeSH
|a Valine: chemistry
650 _ 2 |2 MeSH
|a Valine: metabolism
650 _ 7 |0 0
|2 NLM Chemicals
|a Adrenergic beta-Antagonists
650 _ 7 |0 0
|2 NLM Chemicals
|a Receptors, Adrenergic, beta-2
650 _ 7 |0 13655-52-2
|2 NLM Chemicals
|a Alprenolol
650 _ 7 |0 60-92-4
|2 NLM Chemicals
|a Cyclic AMP
650 _ 7 |0 7004-03-7
|2 NLM Chemicals
|a Valine
650 _ 7 |0 EC 4.6.1.1
|2 NLM Chemicals
|a Adenylate Cyclase
650 _ 7 |2 WoSType
|a J
653 2 0 |2 Author
|a beta(2)-adrenergic receptor
653 2 0 |2 Author
|a valine 114
653 2 0 |2 Author
|a ligand binding
653 2 0 |2 Author
|a site-directed mutagenesis
653 2 0 |2 Author
|a molecular modeling
700 1 _ |0 P:(DE-HGF)0
|a Yanamala, N.
|b 1
700 1 _ |0 P:(DE-HGF)0
|a Upadhyaya, J.
|b 2
700 1 _ |0 P:(DE-HGF)0
|a Halayako, A.
|b 3
700 1 _ |0 P:(DE-Juel1)VDB44599
|a Klein-Seetharaman, J.
|b 4
|u FZJ
700 1 _ |0 P:(DE-HGF)0
|a Chelikani, P.
|b 5
773 _ _ |0 PERI:(DE-600)2000025-X
|a 10.1002/pro.285
|g p. 85 - 93
|p 85 - 93
|q 85 - 93
|t Protein science
|x 0961-8368
|y 2010
856 7 _ |2 Pubmed Central
|u http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2817842
909 C O |o oai:juser.fz-juelich.de:8401
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914 1 _ |y 2010
915 _ _ |0 StatID:(DE-HGF)0010
|a JCR/ISI refereed
920 1 _ |0 I:(DE-Juel1)ISB-2-20090406
|d 31.12.2010
|g ISB
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|l Molekulare Biophysik
|x 0
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981 _ _ |a I:(DE-Juel1)ISB-2-20090406

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