NMR evidence for different conformations of the bioactive region of rat CCK-8 and CCK-58.
Sulfated CCK-58 and CCK-8 have identical bioactive C-terminal primary sequences but distinct C-terminal solution structures and different bioactivities. To examine structural differences in greater detail, rat CCK-58 and -8 were synthesized with isotopic enrichment of C-terminal residues with (15)N at alpha-amino nitrogens. Proton and nitrogen chemical shift assignments of peptide solutions were obtained by homo- and heteronuclear NMR methods. These data show that the tertiary structure ensembles of C-terminal CCK-8 and CCK-58 differ significantly. Thus, distinct solution conformations may explain differences in CCK(A) and CCK(B) receptor interactions of large and small molecular forms of CCK.
Keire
David A
DA
CURE Digestive Diseases Research Center, Greater Los Angeles Veterans Health Care System, Los Angeles, CA 90073, USA. dkeire@ucla.edu
Solomon
Travis E
TE
Reeve
Joseph R
JR
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002766:Cholecystokinin / Q000737:chemistry*; D004285:Dogs; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D051381:Rats; D016415:Sequence Alignment; D012844:Sincalide / Q000737:chemistry*
C038823:cholecystokinin 58; D002766:Cholecystokinin; D012844:Sincalide