Journal article
Inhibitors and fluorescent probes for protein kinase PKAc extgreekb and its S54L mutant, identified in a patient with cortisol producing adenoma
Publication Details
Authors: | Nonga, O.; Enkvist, E.; Herberg, F.; Uri, A. |
Publication year: | 2020 |
Journal: | Bioscience, Biotechnology, and Biochemistry |
Pages range : | 1839-1845 |
Volume number: | 84 |
Issue number: | 9 |
ISSN: | 0916-8451 |
eISSN: | 1347-6947 |
DOI-Link der Erstveröffentlichung: |
Abstract
Recently, a mutation was discovered in the gene PRKACB encoding the catalytic subunit \textgreekb of PKA (PKAc\textgreekb) from a patient with severe Cushing's syndrome. This mutation, S54L, leads to a structural change in the glycine-rich loop of the protein. In the present study, an inhibitor with six-fold selectivity toward S54L-PKAc\textgreekb mutant over the wild-type enzyme was constructed. Moreover, we developed a fluorescent assay allowing to determine side by side the affinity of commercially available PKA inhibitors, newly synthesized compounds, and fluorescent probes toward PKAc\textgreekb and S54L-PKAc\textgreekb.
Recently, a mutation was discovered in the gene PRKACB encoding the catalytic subunit \textgreekb of PKA (PKAc\textgreekb) from a patient with severe Cushing's syndrome. This mutation, S54L, leads to a structural change in the glycine-rich loop of the protein. In the present study, an inhibitor with six-fold selectivity toward S54L-PKAc\textgreekb mutant over the wild-type enzyme was constructed. Moreover, we developed a fluorescent assay allowing to determine side by side the affinity of commercially available PKA inhibitors, newly synthesized compounds, and fluorescent probes toward PKAc\textgreekb and S54L-PKAc\textgreekb.
