Identification of the amino acid residues involved in selective agonist binding in the first extracellular loop of the delta- and mu-opioid receptors.
Effects of amino acid substitutions in the first extracellular loop region of the delta- and mu-opioid receptors were examined. Substitution of lysine-108 of the delta-receptor (delta K108) with asparagine improved affinity to [D-Ala2,MePhe4,Gly-ol5]enk ephalin (DAGO), a mu-selective peptide agonist, to be comparable with that of the mu-receptor. On the other hand, replacement of mN127 with lysine decreased the affinity to DAGO by approximately 15-fold. These results suggest that dK108 and mN127, which correspond to each other in the aligned amino acid sequences, mainly determine the difference in DAGO binding affinity between the delta- and mu-receptors.
Fukuda
K
K
Department of Anesthesia, Kyoto University Hospital, Japan.
Terasako
K
K
Kato
S
S
Mori
K
K
D000595:Amino Acid Sequence; D000700:Analgesics / Q000378:metabolism; D000818:Animals; D001216:Asparagine; D001665:Binding Sites; D001667:Binding, Competitive; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000378:metabolism*; D007700:Kinetics; D008239:Lysine; D008969:Molecular Sequence Data; D009020:Morphine / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D017433:Protein Structure, Secondary; D051381:Rats; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000737:chemistry* / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000737:chemistry* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000819:agonists / Q000737:chemistry / Q000378:metabolism
D000700:Analgesics; D004745:Enkephalins; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D011994:Recombinant Proteins; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D001216:Asparagine; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-; D008239:Lysine