Abstract
Glucagon plays an essential role in the glycemia maintenance during fasting, but also
aggravates hyperglycemia in diabetic patients. A series of analogues of glucagon were
synthesized replacing each amino acid of the C-terminal region (residues 15–29) with
alanine. The residues affecting the binding to the glucagon receptor are found to
be located on one face of the glucagon helix. Several 3-dimensional models of the
N-terminal domain of the glucagon receptor in complex with its ligand peptide were
built and used to analyze the peptide-receptor interface in terms of the nature of
the peptide residues and the interactions they form with the receptor. The models
suggest that glucagon keeps its native helical structure upon binding, and that a
large part of the interface formed with the receptor is hydrophobic. We find that
in the C-terminal region, F22, V23, M27, and D15 are the most important residues for
peptide binding. They bury a large portion of their solvent accessible surface area
and make numerous interactions with the receptor mainly of the hydrophobic type.
Key words
class B receptor - ligand docking - receptor recognition - binding site
