Structural features of human inositol phosphate multikinase rationalize its inositol phosphate kinase and phosphoinositide 3-kinase activities.

ABSTRACT: Human inositol phosphate multikinase (HsIPMK) critically contributes to intracellular signaling through its inositol-1,4,5-trisphosphate (Ins(1,4,5)P₃) 3-kinase and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P₂) 3-kinase activities. This catalytic profile is not conserved; orthologs from Arabidopsis thaliana and Saccharomyces cerevisiae are predominantly Ins(1,4,5)P₃ 6-kinases, and the plant enzyme cannot phosphorylate PtdIns(4,5)P₂ Therefore, crystallographic analysis of the yeast and plant enzymes, without bound inositol phosphates, do not structurally rationalize HsIPMK activities. Here, we present 1.6-Å resolution crystal structures of HsIPMK in complex with either Ins(1,4,5)P₃ or PtdIns(4,

SUBMITTER: Wang H 

PROVIDER: S-EPMC5672042 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature