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The glucagon‐like peptide‐1 receptor binding site for the N‐terminus of GLP‐1 requires polarity at Asp198 rather than negative charge
Author(s) -
López de Maturana Rakel,
Donnelly Dan
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)03492-0
Subject(s) - peptide , receptor , chemistry , polarity (international relations) , agonist , mutation , affinities , glucagon like peptide 1 , glucagon like peptide 1 receptor , binding site , glucagon , biochemistry , n terminus , biophysics , biology , peptide sequence , endocrinology , hormone , cell , gene , type 2 diabetes , diabetes mellitus
The mutation of Asp198 to Asn in the receptor for glucagon‐like peptide‐1(7–36)amide (GLP‐1) had no effect upon GLP‐1 affinity whereas substitution with Ala greatly reduced affinity, demonstrating the importance of polarity rather than negative charge at Asp198. However, the Asp198‐Ala mutation had less effect upon the affinity of Exendin‐4, a peptide agonist that has been shown previously not to require its N‐terminus for high affinity. Moreover, the affinity of a truncated GLP‐1 analogue lacking the first eight residues was not affected by the Asp198‐Ala mutation, demonstrating that Asp198 is required for maintaining the binding site of the N‐terminal region of GLP‐1.