Capillary electrophoresis mass spectrometry (CE-MS) allows for the rapid and accurate quantitative analysis of inositol phosphates (InsPs) and inositol pyrophosphates (PP-InsPs). The recent discovery ...

We report “Sirtuin Trapping Ligands” (SirTraps), mechanism-based 1,2,3-triazole inhibitors that hijack sirtuin (SIRT) catalysis to form covalent triazolium– or triazole–ADP-ribose (ADPR) adducts from...

Author summary Inositol pyrophosphates (PP-InsPs) are eukaryote-specific cellular messengers that control a plethora of critical physiological processes, ranging from cellular metabolism to cellular e...

Inorganic polyphosphate (polyP), a linear biopolymer composed only of orthophosphate units, has emerged as a molecule of critical biological importance across species. While commercially available pol...

Inositol pyrophosphates (PP-InsPs) are highly phosphorylated signaling molecules that regulate diverse cellular processes, including phosphate homeostasis and energy metabolism across species. Despit...

Phosphorylated myo-inositols (InsPs) are essential cytoplasmic signaling molecules, while their lipidated analogs (PtdInsPs) play a crucial role in membrane signaling. Stereoselective synthesis of the...

Inorganic polyphosphate (polyP) is a ubiquitous biopolymer composed of multiple orthophosphates connected by energy-rich phosphoanhydride bonds. In organisms, polyP is digested by two types of enzymes...

Inositol phosphates control many central processes in eukaryotic cells including nutrient availability, growth, and motility. Kinetic resolution of a key modulator of their signaling functions, the turnover of the phosphate groups on the inositol ring, has been hampered by slow uptake, high dilution, and constraining growth conditions in radioactive pulse-labeling approaches. Here, we demonstrate a rapid (seconds to minutes) and nonradioactive labeling strategy of inositol polyphosphates through 18O-water in yeast, human cells, and amoeba, which can be applied in any media. In combination with capillary electrophoresis and mass spectrometry, 18O-water labeling simultaneously dissects the in vivo phosphate group dynamics of a broad spectrum of even rare inositol phosphates. The good temporal resolution allowed us to discover vigorous phosphate group exchanges in some inositol polyphosphates and pyrophosphates, whereas others remain remarkably inert. We propose a model in which the biosynthetic pathway of inositol polyphosphates and pyrophosphates is organized in distinct, kinetically separated pools. While transfer of compounds between those pools is slow, each pool undergoes rapid internal phosphate cycling. This might enable the pools to perform distinct signaling functions while being metabolically connected.

Peptides are highly selective organocatalysts, with intrinsic modularity allowing precise control over structure and function. Advances in peptide synthesis, biotechnology, and cheminformatics will en...

Phosphorylated myo-inositols (InsPs) are essential cytoplasmic signaling molecules, while their lipidated analogs (PtdInsPs) play a crucial role in membrane signaling. Stereoselective synthesis of the...

Inositol pyrophosphates are key effectors of eukaryal cellular phosphate homeostasis. They are synthesized by kinases that add a β-phosphate to the 5- or 1-phosphate groups of IP6 and catabolized by t...

Inositol pyrophosphates (PP-InsPs) are highly phosphorylated signaling molecules that regulate diverse cellular processes, including phosphate homeostasis and energy metabolism across species. Despite...

The phosphate exporter XPR1 is essential for maintenance of cellular phosphate levels. Here authors present cryo-EM structures of XPR1 that reveal how binding of the signaling molecule 1,5-InsP8 to it...

Inositol phosphates (IPs) and inositol pyrophosphate play critical roles in many biological processes as signaling molecules in pathways responsible f…

This study reports the first substrate-bound structures of polyphosphate kinase 2-II (PPK2-II) enzymes, offering insights into nucleoside diphosphate (NDP) synthesis. BcPPK2 (Bacillus cereus) and LfP....

Inorganic polyphosphate (polyP) is a ubiquitous biopolymer composed of multiple orthophosphates connected by energy-rich phosphoanhydride bonds. In organisms, polyP is digested by two types of enzymes...

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