Pituitary adenylate cyclase activating polypeptide is a potent calmodulin inhibitor.
We report here that pituitary adenylate cyclase activating polypeptide (PACAP38), a new 38-residue neuropeptide of the secretin/glucagon family, is a potent inhibitor of calmodulin in vitro in the activation of bovine brain calmodulin-dependent cyclic nucleotide phosphodiesterase. The concentration of PACAP38 for half-maximal inhibition of the phosphodiesterase is 15 nM, one of the lowest for known calmodulin inhibitors. In the presence of Ca2+, PACAP38 binds strongly to calmodulin in a 1:1 ratio with a dissociation constant of about 28 nM. The binding is not dissociated by 4 M urea. In the absence of Ca2+ the binding is at random and can be dissociated by 4 M urea. Studies with PACAP38 derivatives show that the carboxyl half of the PACAP38 molecule is essential for the inhibition of calmodulin.
Au
T K
TK
Department of Zoology, University of Hong Kong.
Leung
P C
PC
D000818:Animals; D001921:Brain / Q000201:enzymology*; D002147:Calmodulin / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D002417:Cattle; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D009479:Neuropeptides / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011485:Protein Binding
D002147:Calmodulin; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D010727:Phosphoric Diester Hydrolases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1