A small signaling domain controls PPIP5K phosphatase activity in phosphate homeostasis.

ABSTRACT: Inositol pyrophosphates (PP-InsPs) are eukaryotic nutrient messengers. The N-terminal kinase domain of diphosphoinositol pentakisphosphate kinase (PPIP5K) generates the messenger 1,5-InsP₈, the C-terminal phosphatase domain catalyzes PP-InsP breakdown. The balance between kinase and phosphatase activities regulates 1,5-InsP₈ levels. Here, we present crystal structures of the apo and substrate-bound PPIP5K phosphatase domain from S. cerevisiae (ScVip1^PD). ScVip1^PD is a phytase-like inositol 1-pyrophosphate histidine phosphatase with two conserved catalytic motifs. The enzyme has a strong preference for 1,5-InsP₈ and is inhibited by inorganic phosphate. It contains an α-helical insertion domain stabilized by a structural Zn²⁺

SUBMITTER: Raia P 

PROVIDER: S-EPMC11836120 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature