Document Type
Article
Publication Title
Journal of Biological Chemistry
Publication Date
6-26-1998
Volume
273
Issue
26
Disciplines
Biology | Life Sciences
Abstract
The active sites of guanylyl and adenylyl cyclases are closely related. The crystal structure of adenylyl cyclase and modeling studies suggest that specificity for ATP or GTP is dictated in part by a few amino acid residues, invariant in each family, that interact with the purine ring of the substrate. By exchanging these residues between guanylyl cyclase and adenylyl cyclase, we can completely change the nucleotide specificity of guanylyl cyclase and convert adenylyl cyclase into a nonselective purine nucleotide cyclase. The activities of these mutant enzymes remain fully responsive to their respective stimulators, sodium nitroprusside and G(s)α. The specificity of nucleotide inhibitors of guanylyl and adenylyl cyclases that do not act competitively with respect to substrate are similarly altered, indicative of their action at the active sites of these enzymes.
DOI
https://doi.org/10.1074/jbc.273.26.16332
Rights
© 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Sunahara, R. K.; Beuve, A.; Tesmer, J. J.G.; Sprang, S. R.; Garbers, D. L.; and Gilman, A. G., "Exchange of substrate and inhibitor specificities between adenylyl and guanylyl cyclases" (1998). Biological Sciences Faculty Publications. 534.
https://scholarworks.umt.edu/biosci_pubs/534