Biochemical and structural characterization of an inositol pyrophosphate kinase from a giant virus

Guangning Zong, Yann Desfougères, Paloma Portela-Torres, Yong Uk Kwon, Adolfo Saiardi, Stephen B. Shears, Huanchen Wang

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


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.

Original languageEnglish
Pages (from-to)462-480
Number of pages19
JournalEMBO Journal
Issue number3
StatePublished - 1 Feb 2024

Bibliographical note

Publisher Copyright:
© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024.


  • Cell Signaling
  • Giant Virus
  • Inositol Phosphate
  • Kinase
  • Phosphate Geochemistry


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