Three phosphatase families form a community: The phosphohydrolases that act upon inositol pyrophosphates

Abstract

Inositol pyrophosphates (PP-InsP) are high energy signaling molecules that play important roles in eukaryotes. They are synthesized from inositol polyphosphates by kinases that add a diphosphate (β phosphate) at one or more positions on the myo-inositol ring. The focus of this review is on the phosphatases specific for the β phosphate. These enzymes are members of three different families of phosphohydrolases: the histidine acid phosphatase family that is specific for β phosphate on 1C, the cysteine phosphatase family that is specific for the diphosphate on 5C, and the Nudix family that is promiscuous both in terms of the position of the diphosphate on PP-InsPs and recognition of a range of molecules with phosphoanhydride linkages. These three families of phosphatases share overlapping PP-InsP substrates, and as a community of enzymes they have a combined influence on PP-InsP pools, impacting cellular processes and phenotypes. Each phosphatase family is discussed from biochemical perspectives (enzyme structure, substrate preferences, kinetic properties), distribution across eukaryotes (evolutionary, phylogenetic), and the similarities and differences in the affected cellular processes across fungi, animals, and plants.