Recently, a mutation was discovered in the gene PRKACB encoding the catalytic subunit β of PKA (PKAcβ) 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-PKAcβ 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 PKAcβ and S54L-PKAcβ.

中文翻译：

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蛋白激酶PKAcβ及其S54L突变体的抑制剂和荧光探针已在患有皮质醇的腺瘤患者中确定。

最近，在来自患有严重库欣氏综合症的患者的编码PRKA的催化亚基β（PKAcβ）的基因PRKACB中发现了突变。S54L这种突变导致蛋白质的富含甘氨酸的环发生结构变化。在本研究中，构建了一种对S54L-PKAcβ突变体的选择性比野生型酶高六倍的抑制剂。此外，我们开发了一种荧光测定法，可以并行确定市售PKA抑制剂，新合成的化合物和荧光探针对PKAcβ和S54L-PKAcβ的亲和力。