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Biochemical and structural characterization of an inositol pyrophosphate kinase from a giant virus
- Title
- Biochemical and structural characterization of an inositol pyrophosphate kinase from a giant virus
- Authors
- Zong; Guangning; Desfougères; Yann; Portela-Torres; Paloma; Kwon; Yong-Uk; Saiardi; Adolfo; Stephen B.; Wang; Huanchen; Shears
- Ewha Authors
- 권용억
- SCOPUS Author ID
- 권용억
![scopus](/images/layout/icon2.png)
- Issue Date
- 2024
- Journal Title
- EMBO Journal
- ISSN
- 0261-4189
- Citation
- EMBO Journal vol. 43, no. 3, pp. 462 - 480
- Keywords
- Cell Signaling; Giant Virus; Inositol Phosphate; Kinase; Phosphate Geochemistry
- Publisher
- Springer Nature
- Indexed
- SCIE; SCOPUS
![scopus](/images/layout/scopus2.gif)
- Document Type
- Article
- 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. © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024.
- DOI
- 10.1038/s44318-023-00005-0
- Appears in Collections:
- 자연과학대학 > 화학·나노과학전공 > Journal papers
- Files in This Item:
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zong-et-al-2024-biochemical-and-structural-characterization-of-an-inositol-pyrophosphate-kinase-from-a-giant-virus.pdf(7.76 MB)
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