ArticleThe EMBO journal2024
Biochemical and structural characterization of an inositol pyrophosphate kinase from a giant virus.
Article in The EMBO journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 10 citations in OpenAlex.
- Structural insights into the development of inhibitors for inositol phosphate kinases.FEBS letters · 2026Review
- Enabling Technologies for the Dissection of Inositol Pyrophosphate Physiology.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
- Visualizing and Identifying Inositol Pyrophosphate Isomers in Crystallo.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Analysis of Inositol Phosphates, Diphosphoinositol Phosphates, and Their Analogs by HPLC on an Acid-Compatible Stationary Phase with Detection by Complexation with Ferric Ion.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Interaction with IP6K1 supports pyrophosphorylation of substrate proteins by the inositol pyrophosphate 5-InsP7.Bioscience reports · 2024Article
- Origin, evolution, and diversification of inositol 1,4,5-trisphosphate 3-kinases in plants and animals.BMC genomics · 2024Article
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
Kinases that synthesize inositol phosphates (IPs) and pyrophosphates (PP-IPs) control numerous biological processes in eukaryotic cells. Herein, we extend this cellular signaling repertoire to viruses. We have biochemically and structurally characterized a minimalist inositol phosphate kinase (i.e., TvIPK) encoded by Terrestrivirus, a nucleocytoplasmic large ("giant") DNA virus (NCLDV). We show that TvIPK can synthesize inositol pyrophosphates from a range of scyllo- and myo-IPs, both in vitro and when expressed in yeast cells. We present multiple crystal structures of enzyme/substrate/nucleotide complexes with individual resolutions from 1.95 to 2.6 Å. We find a heart-shaped ligand binding pocket comprising an array of positively charged and flexible side chains, underlying the observed substrate diversity. A crucial arginine residue in a conserved "G-loop" orients the γ-phosphate of ATP to allow substrate pyrophosphorylation. We highlight additional conserved catalytic and architectural features in TvIPK, and support their importance through site-directed mutagenesis. We propose that NCLDV inositol phosphate kinases may have assisted evolution of inositol pyrophosphate signaling, and we discuss the potential biogeochemical significance of TvIPK in soil niches.
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Registered trials
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