Protein kinase allosteric site mutations!
The atypical mammalian protein kinase ALPK1 is activated by nucleoside diphosphate heptoses, switching on a signal transduction pathway of the innate immune system.
Mutations in ALPK1, first identified in 2019, cause a genetic disorder, termed ‘ROSAH syndrome,’ and a rare type of tumour called ‘spiradenoma.’
Recently, these ALPK1 mutations were found to cause activation of ALPK1 by several endogenous human nucleoside diphosphate sugars, leading to chronic inflammatory signalling without infection.
ROSAH syndrome and spiradenoma might be the first examples of diseases caused by altered specificity of an enzyme for its allosteric activators, suggesting ways in which drugs could be developed to inhibit these ALPK1 mutants selectively without compromising the innate immune system.
https://www.cell.com/trends/biochemical-sciences/fulltext/S0968-0004(24)00233-0
