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Adenosine Inhibition of Calmodulin‐Sensitive Adenylate Cyclase from Bovine Cerebral Cortex
Author(s) -
Yeager Robert E.,
Nelson Richard,
Storm Daniel R.
Publication year - 1986
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1986.tb02841.x
Subject(s) - adenosine , adenylate kinase , cyclase , biochemistry , enzyme , purine , gtp' , chemistry , calmodulin , non competitive inhibition , adenosine monophosphate , nucleotide , gene
Calmodulin (CaM)‐sensitive adenylate cyclase has recently been purified extensively from bovine brain. In this study, the sensitivity of the CaM‐sensitive adenylate cyclase to adenosine and adenosine analogs was examined. The highly purified enzyme preparation retained sensitivity to inhibition by adenosine and adenosine analogs with ribose ring modifications, but not to those with purine ring modifications. Adenosine inhibition of this enzyme was not dependent on GTP and was noncompetitive with respect to ATP. Enzyme that had been dissociated from functional guanine nucleotide binding protein interactions by gel filtration in the presence of the zwitterionic detergent 3‐[3‐(cholamido‐propyl)‐dimethylammonio]‐propanesulfonate and Mn 2+ retained sensitivity to adenosine inhibition. The K i for adenosine inhibition of the CaM‐sensitive adenylate cyclase was approximately 2.6 × 10 ‐4 M . 5′‐Guanylylimi‐dodiphosphate and CaM did not affect the K i of 3′‐deoxy‐adenosine for the enzyme, but the presence of Ca 2+ in the millimolar range raised the K i by a factor of 5. These results show that the CaM‐sensitive form of adenylate cyclase from bovine brain is subject to adenosine inhibition, and strongly suggest that this inhibition is due to interaction of ligands with a purine‐specific (“P”) site located on the catalytic subunit of the enzyme.