Abstract
A mutagenesis study to systematically analyse residues spanning the first extracellular loop of the GLP-1 receptor identified a double mutant, Met-204/Tyr-205-Ala/Ala, which displayed: markedly reduced affinity for the natural agonist GLP-1; slightly reduced affinity for its analogue exendin-4; and unaltered affinity for several N-terminally truncated analogues of GLP-1 and exendin-4. This suggests that the locus is important for the formation of the binding site for the N-terminal residues of peptide agonists.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Cell Line
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Cyclic AMP / metabolism
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Exenatide
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Gene Expression Regulation
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Glucagon / chemistry
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Glucagon / genetics
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Glucagon / metabolism*
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Glucagon / pharmacology
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Glucagon-Like Peptide 1
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Glucagon-Like Peptide-1 Receptor
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Humans
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Inhibitory Concentration 50
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Ligands
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Methionine / genetics
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Methionine / metabolism*
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Molecular Sequence Data
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Peptide Fragments / chemistry
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Peptide Fragments / genetics
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Peptide Fragments / metabolism*
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Peptide Fragments / pharmacology
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Peptides / chemistry
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Peptides / genetics
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Peptides / metabolism*
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Peptides / pharmacology
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Protein Precursors / chemistry
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Protein Precursors / genetics
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Protein Precursors / metabolism*
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Protein Precursors / pharmacology
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Rats
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Receptors, Glucagon / agonists*
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Receptors, Glucagon / genetics
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Receptors, Glucagon / metabolism*
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Sequence Alignment
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Sequence Deletion / genetics
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Tyrosine / genetics
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Tyrosine / metabolism*
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Venoms / chemistry
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Venoms / genetics
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Venoms / metabolism*
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Venoms / pharmacology
Substances
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GLP1R protein, human
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Glp1r protein, rat
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Glucagon-Like Peptide-1 Receptor
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Ligands
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Peptide Fragments
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Peptides
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Protein Precursors
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Receptors, Glucagon
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Venoms
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Tyrosine
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Glucagon-Like Peptide 1
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Glucagon
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Exenatide
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Methionine
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Cyclic AMP