ArticleChemistry (Weinheim an der Bergstrasse, Germany)2016
Cellular Cations Control Conformational Switching of Inositol Pyrophosphate Analogues.
Article in Chemistry (Weinheim an der Bergstrasse, Germany), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Structural insights into the development of inhibitors for inositol phosphate kinases.FEBS letters · 2026Review
- Inositol pyrophosphate kinases in health and disease.FEBS letters · 2026Review
- Protein pyrophosphorylation by inositol pyrophosphates - detection, function, and regulation.FEBS letters · 2026Review
- The Diphosphoinositol Polyphosphate Phosphohydrolase 1 family binds IPInternational journal of biological macromolecules · 2026Article
- Proteome-wide quantification of inositol pyrophosphate-protein interactions.Nature communications · 2026Article
- Expanding the Inositol Pyrophosphate Toolbox: Stereoselective Synthesis and Application of PP-InsPAngewandte Chemie (International ed. in English) · 2025Article
- Visualizing and Identifying Inositol Pyrophosphate Isomers in Crystallo.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Inositol Phosphate Kinase Architecture: Practical Approaches and Lessons Learned.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Enabling Technologies for the Dissection of Inositol Pyrophosphate Physiology.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Synthesis of Unsymmetrical Difluoromethylene Bisphosphonates.Organic letters · 2024Article
- Human plasma inositol hexakisphosphate (InsPmicroPublication biology · 2024Article
- Fluorination Influences the Bioisostery of Myo-Inositol Pyrophosphate Analogs.Chemistry (Weinheim an der Bergstrasse, Germany) · 2023Article
- Inositol pyrophosphates activate the vacuolar transport chaperone complex in yeast by disrupting a homotypic SPX domain interaction.Nature communications · 2023Article
- One Scaffold, Two Conformations: The Ring-Flip of the Messenger InsPBiomolecules · 2023Article
- 5-IPNature metabolism · 2021Article
- Dissecting the activation of insulin degrading enzyme by inositol pyrophosphates and their bisphosphonate analogs.Chemical science · 2021Article
- Rapid stimulation of cellular Pi uptake by the inositol pyrophosphate InsPChemical science · 2020Article
- Metabolism and Functions of Inositol Pyrophosphates: Insights Gained from the Application of Synthetic Analogues.Molecules (Basel, Switzerland) · 2020Review
- Control of XPR1-dependent cellular phosphate efflux by InsPProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Synthesis of an α-phosphono-α,α-difluoroacetamide analogue of the diphosphoinositol pentakisphosphate 5-InsPMedChemComm · 2019Article
Corrections and comments
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Authors and funding
7 authors.
Funding
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. Remarkably, the presence of potassium and magnesium ions enabled the analogues to adopt two different conformations near physiological pH. Understanding how the intrinsic chemical properties of the PP-InsPs can contribute to their complex signalling outputs will be essential to elucidate their regulatory functions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.