A high energy phosphate jump - From pyrophospho-inositol to pyrophospho-serine

Inositol Pyrophosphates: Signaling Molecules with Pleiotropic Actions in Mammals

“…Indeed, PP-IPs can non-enzymatically transfer their β-phosphates to serine residues that have been primed by phosphorylation by CK2. In this manner, CK2 provides the phosphoprotein substrates for PP-IP-mediated pyrophosphorylation because acidic amino acids surrounding the targeted phospho-Ser correspond to the consensus motif for CK2 [33,34,40]. PP-IPs' protein pyrophosphorylation appears to be involved in many biological events, such as glycolysis [41], HIV particle release [42], and dynein-mediated trafficking [43].…”

Metabolism and Functions of Inositol Pyrophosphates: Insights Gained from the Application of Synthetic Analogues

“…This is a situation in which metabolically stable PP-InsP analogs can be helpful, particularly with regards to biochemical and cellular assays, in which the natural PP-InsPs have a short half-life due to their inherently fast turnover rate [ 20 , 21 ]. Another application for such research tools is to distinguish between the two molecular mechanisms by which protein function can be modulated by the PP-InsPs: allosteric regulation upon ligand binding, versus covalent regulation by non-enzymic phosphotransfer [ 1 , 6 , 7 , 8 , 22 ]. The latter cannot be mimicked by metabolically stable PP-InsP analogs.…”

Rapid stimulation of cellular Pi uptake by the inositol pyrophosphate InsP8induced by its photothermal release from lipid nanocarriers using a near infra-red light-emitting diode

“…These polyphosphate assemblies represent a thermodynamically favorable springboard from which a b-phosphate can be non-enzymatically transferred to a preexisting phospho-serine residue that lies within an appropriately acidic protein microenvironment; 1,2 this unique mechanism of covalent modication -'pyrophosphorylation' 2regulates the functions of a number of proteins that control diverse biological processes. 3 In addition, the chemical synthesis and application of non-hydrolysable methylene bisphosphonate (PCP-) bioisosteres of the PP-InsPs has helped to demonstrate that this class of cellular signals also regulate cellular physiology through alternate, allosteric modication of protein activities. [4][5][6] The biological consequences of both of these mechanisms of action of PP-InsPs are being studied in yeasts, plant and animal cells, and there is a growing focus on their regulation of metabolic balance, particularly with regards to cellular homeostasis of inorganic phosphate (Pi).…”