8T8V

Crystal structure of Terrestrivirus inositol pyrophosphate kinase in complex with ADP

8T8V の概要

• エントリーDOI: 10.2210/pdb8t8v/pdb
• 分子名称: Kinase, ADENOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: virus, kinase, inositol phosphate, myo-inositol, soil, viral protein
• 由来する生物種: Terrestrivirus sp.
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29354.32

構造登録者

Zong, G.,Wang, H.,Shears, S.B. (登録日: 2023-06-23, 公開日: 2023-11-15, 最終更新日: 2024-02-14)

主引用文献

Zong, G.,Desfougeres, Y.,Portela-Torres, P.,Kwon, Y.U.,Saiardi, A.,Shears, S.B.,Wang, H.
Biochemical and structural characterization of an inositol pyrophosphate kinase from a giant virus.
Embo J., 43:462-480, 2024

PubMed 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.

PubMed: 38216735
DOI: 10.1038/s44318-023-00005-0

実験手法

X-RAY DIFFRACTION (1.96 Å)