Cellular Cations Control Conformational Switching of Inositol Pyrophosphate Analogues.

ABSTRACT: The inositol pyrophosphate messengers (PP-InsPs) are emerging as an important class of cellular regulators. These molecules have been linked to numerous biological processes, including insulin secretion and cancer cell migration, but how they trigger such a wide range of cellular responses has remained unanswered in many cases. Here, we show that the PP-InsPs exhibit complex speciation behaviour and propose that a unique conformational switching mechanism could contribute to their multifunctional effects. We synthesised non-hydrolysable bisphosphonate analogues and crystallised the analogues in complex with mammalian PPIP5K2 kinase. Subsequently, the bisphosphonate analogues were used to investigate the protonation sequence, metal-coordination properties, and conformation in solution. Rema

SUBMITTER: Hager A 

PROVIDER: S-EPMC5076471 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature