Untangling Inositol (Pyro)Phosphate Biology Through Emerging Technologies

Inositol (pyro)phosphates represent a vital class of intracellular messengers that govern multiple biological processes. The last decade has experienced a surge of interest in the functions of this c...

advanced.onlinelibrary.wiley.com

Affinity‐Based Interactome Mapping of Inositol Pyrophosphates Reveals 4/6‐PP‐InsP5‐Binding Proteins in Plants

Inositol pyrophosphates (PP-InsPs) are central regulators of eukaryotic signaling events. While certain PP-InsP isomers have been conclusively linked to the regulation of phosphate homeostasis throug...

advanced.onlinelibrary.wiley.com

onlinelibrary.wiley.com

Establishing 18O-Labeled Inositol Phosphates for Quantitative Capillary Electrophoresis-Mass Spectrometry: Fragmentation Pathways and Comparison with 13C-Labeled Analogs

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 ...

pubs.acs.org

From Pharmacophore to Warhead: NAD+‐Targeting Triazoles as Mechanism‐Based Sirtuin Inhibitors

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...

onlinelibrary.wiley.com

Conservation of heat stress acclimation by the IPK2-type kinases that control the synthesis of the inositol pyrophosphate 4/6-InsP7 in land plants

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...

journals.plos.org

Synthesis of monodisperse inorganic polyphosphate polyP10 via a photocaging strategy

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...

pubs.rsc.org

Expanding the Inositol Pyrophosphate Toolbox: Stereoselective Synthesis and Application of PP‐InsP4 Isomers in Plant Signaling

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

doi.org

Stereoselective chemoenzymatic phytate transformations provide access to diverse inositol phosphate derivatives

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...

pubs.rsc.org

A Screening Approach Unveils an Unknown Mn2+-dependent Endopolyphosphatase Activity in Yeast

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...

pubs.rsc.org

Pools of Independently Cycling Inositol Phosphates Revealed by Pulse Labeling with 18O-Water

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.

pubs.acs.org

Peptide catalysis: Trends and opportunities

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

cell.com

Stereoselective chemoenzymatic phytate transformations provide access to diverse inositol phosphate derivatives

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...

chemrxiv.org

Tandem inactivation of inositol pyrophosphatases Asp1, Siw14, and Aps1 illuminates functional redundancies in inositol pyrophosphate catabolism in fission yeast | mBio

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...

journals.asm.org

Expanding the PP-INSP₄ Toolbox: Synthesis, Stereochemical Assignment, and Application in Plant Phosphate Signaling

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

chemrxiv.org

Transport and InsP8 gating mechanisms of the human inorganic phosphate exporter XPR1 - Nature Communications

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...

nature.com

Biochemical and biophysical characterization of inositol-tetrakisphosphate 1-kinase inhibitors

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

sciencedirect.com

Structural Insights into Broad‐Range Polyphosphate Kinase 2‐II Enzymes Applicable for Pyrimidine Nucleoside Diphosphate Synthesis

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....

doi.org

A Screening Approach Unveils an Unknown Mn2+-dependent Endopolyphosphatase Activity in Yeast

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...

biorxiv.org

KIDINS220 and InsP8 safeguard the stepwise regulation of phosphate exporter XPR1

biorxiv.org

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