The detection, purification, structural characterization, and metabolism of diphosphoinositol pentakisphosphate(s) and bisdiphosphoinositol tetrakisphosphate(s).

Affinity‐based proteomics reveals novel targets of inositol pyrophosphate (5‐IP7)‐dependent phosphorylation and binding in Trypanosomacruzi replicative stages

“…We found no significant differences in the relative abundance of IP 6 when compared with that of 5‐IP 7 in epimastigote forms. The 5‐IP 7 levels determined (2.9 ± 0.4 µM) for epimastigote forms are similar to those measured in embryonic fibroblast cells (NIH 3T3), but 20‐fold lower than those reported for the ameba Dictyostelium (5–250 µM) (Stephens et al., 1993). In most organisms, levels of IP 6 are considerably higher than those of 5‐IP 7 , and such relation was only evidenced in the intracellular stage, amastigote.…”

“…This signaling pathway was the first direct evidence of IP‐mediated processes through protein binding (Berridge, 2009). IP 3 can be further phosphorylated at different hydroxyl positions producing the fully phosphorylated form known as inositol hexakisphosphate (IP 6 ) or phytic acid, which can be a precursor of the inositol pyrophosphates (Stephens et al., 1993). Inositol pyrophosphates are characterized by the presence of one (PP‐IP 4 and PP‐IP 5 ) or two (PP 2 ‐IP 3 and PP 2 ‐IP 4 ) pyrophosphate moieties at different positions of the myo ‐inositol scaffold (Saiardi et al., 2018).…”

Triplexed Affinity Reagents to Sample the Mammalian Inositol Pyrophosphate Interactome

“…The fact that all of these enzymes were enriched then raises the question whether our dataset contains additional PP-InsP-metabolizing enzymes that have not been previously characterized. PP-InsPs were shown to turn over rapidly in cells, so the presence of additional phosphohydrolases appears reasonable (Caffrey et al, 2000;Stephens et al, 1993). For example, in S. cerevisiae, an additional phosphatase that hydrolyzes the diphosphate groups of PP-InsPs has been discovered: dual-specificity phosphatase Siw14 (synthetic interaction with whi2) (Steidle et al, 2016).…”

Inositol Pyrophosphates Get the Vip1 Treatment

“…The fully phosphorylated six-carbon ring of IP 6 (phytic acid) was thought to represent the end point of inositol phosphorylation. The discovery of inositol phosphate species with seven (diphosphoinositol pentakisphosphate; PP-IP 5 ; IP 7 ) or eight phosphates (bis-diphosphoinositol tetrakisphosphate; [PP] 2 -IP 4 ; IP 8 ) on the inositol ring was exciting and unexpected (Menniti et al, 1993;Stephens et al, 1993). These "high-energy" molecules have been linked to a wide range of biological functions, including vesicle traf-ficking, apoptosis, DNA repair, telomere maintenance, and the stress response (Bennett et al, 2006).…”