A1 adenosine receptors. Two amino acids are responsible for species differences in ligand recognition
| Autor: | A L, Tucker, A S, Robeva, H E, Taylor, D, Holeton, M, Bockner, K R, Lynch, J, Linden |
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| Rok vydání: | 1994 |
| Předmět: |
Adenosine
Binding Sites Recombinant Fusion Proteins Molecular Sequence Data Restriction Mapping Receptors Purinergic P1 Kidney Ligands Transfection Protein Structure Secondary Cell Line Kinetics Dogs Oligodeoxyribonucleotides Species Specificity Chlorocebus aethiops Mutagenesis Site-Directed Animals Cattle Amino Acid Sequence Cloning Molecular Ribosomes |
| Zdroj: | The Journal of biological chemistry. 269(45) |
| ISSN: | 0021-9258 |
| Popis: | Species differences in ligand binding to A1 adenosine receptors were localized to the seventh transmembrane (TM7) region based on the binding of [8-3H]cyclopentyl-1, 3-dipropylxanthine and three other ligands to wild type and six bovine/canine interspecies receptor chimeras expressed in COS-1 cells. Subsequent site-directed mutagenesis experiments identified amino acid 270 (isoleucine/methionine, bovine/canine) as being primarily responsible for species differences in the binding of N6-adenine-substituted compounds, R-N6-phenylisopropyladenosine (R-PIA) and (S)-N6-endonorbornan-2-yl-9-methyladenine, and the C-8-substituted xanthine, [3H]cyclopentyl-1,3-dipropylxanthine. These data are consistent with the hypothesis that the N6 region of adenines and the C-8-region of xanthines bind to the same region of the receptor. A second TM7 amino acid, 277 (serine/threonine, bovine/canine), selectively influences the binding of the ribose-substituted adenosine analog, 5'-N-ethylcarboxamidoadenosine to a variable extent, depending on the nature of amino acid 270. We hypothesize that amino acid 270 of the A1 receptor interacts with the N6 region of adenosine, while amino acid 277 is important, especially in the absence of an N6 substitution, for interactions with a distinct nucleoside region, possibly on the ribose. |
| Databáze: | OpenAIRE |
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