Identical primary sequence but different conformations of the bioactive regions of canine CCK-8 and CCK-58.
The C-terminal bioactive regions of CCK-8 and CCK-58 are identical (DY*MGWMDF-NH(2), Y* denotes a sulfated tyrosine residue), but these peptides have different patterns of bioactivity. Specifically, CCK-58 binds more avidly to the CCK(A) receptor while CCK-8 is more potent for stimulation of amylase secretion from pancreatic acini. We postulate that these seemingly contradictory observations reflect a stable conformational change in CCK-58 that enhances binding, but diminishes activation of second messenger. We used CD and NMR spectra to evaluate postulated structural differences between CCK-8 and the carboxy-terminus of synthetic CCK-58. The CD spectra indicate the presence of turns in CCK-8 but a mixture of helical and random coil structures for CCK-58. Comparisons of partial NMR chemical shift assignments of CCK-58 and full assignments for CCK-8 also indicate differences in the backbone conformations for these residues. The data support the hypothesis that these peptides have different, stable, carboxy-terminal structures that may influence bioactivity.
Keire
D A
DA
CURE Digestive Diseases Research Center, Greater Los Angeles Veterans Health Care System, Los Angeles, California 90073, USA.
Solomon
T E
TE
Reeve
J R
JR
D000818:Animals; D002766:Cholecystokinin / Q000737:chemistry*; D002942:Circular Dichroism; D004285:Dogs; D009682:Magnetic Resonance Spectroscopy; D010446:Peptide Fragments / Q000737:chemistry; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012844:Sincalide / Q000737:chemistry*
D010446:Peptide Fragments; C038823:cholecystokinin 58; D002766:Cholecystokinin; D012844:Sincalide