9GRH

Crystal structure of the C-terminal phosphatase domain from Saccharomyces cerevisiae Vip1 (apo)

9GRH の概要

• エントリーDOI: 10.2210/pdb9grh/pdb
• 分子名称: Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase, ZINC ION (2 entities in total)
• 機能のキーワード: inositol pyrophosphate, inositol pyrophosphate phosphatase, histidine acid phosphatase, phytase, enzyme mechanism, gaf domain, phosphate homeostasis, biosynthetic protein
• 由来する生物種: Saccharomyces cerevisiae (brewer's yeast)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 263416.14

構造登録者

Raia, P.,Lee, K.,Hothorn, M. (登録日: 2024-09-11, 公開日: 2025-02-26)

主引用文献

Raia, P.,Lee, K.,Bartsch, S.M.,Rico-Resendiz, F.,Portugal-Calisto, D.,Vadas, O.,Panse, V.G.,Fiedler, D.,Hothorn, M.
A small signaling domain controls PPIP5K phosphatase activity in phosphate homeostasis.
Nat Commun, 16:1753-1753, 2025

PubMed Abstract: Inositol pyrophosphates (PP-InsPs) are eukaryotic nutrient messengers. The N-terminal kinase domain of diphosphoinositol pentakisphosphate kinase (PPIP5K) generates the messenger 1,5-InsP, the C-terminal phosphatase domain catalyzes PP-InsP breakdown. The balance between kinase and phosphatase activities regulates 1,5-InsP levels. Here, we present crystal structures of the apo and substrate-bound PPIP5K phosphatase domain from S. cerevisiae (ScVip1). ScVip1 is a phytase-like inositol 1-pyrophosphate histidine phosphatase with two conserved catalytic motifs. The enzyme has a strong preference for 1,5-InsP and is inhibited by inorganic phosphate. It contains an α-helical insertion domain stabilized by a structural Zn binding site, and a unique GAF domain that channels the substrate to the active site. Mutations that alter the active site, restrict the movement of the GAF domain, or change the substrate channel's charge inhibit the enzyme activity in vitro, and Arabidopsis VIH2 in planta. Our work reveals the structure, enzymatic mechanism and regulation of eukaryotic PPIP5K phosphatases.

PubMed: 39966396
DOI: 10.1038/s41467-025-56937-0

実験手法

X-RAY DIFFRACTION (3.2 Å)