Disorder-to-order active site capping regulates the rate-limiting step of the inositol pathway.

ABSTRACT: Myo-inositol-1-phosphate synthase (MIPS) catalyzes the NAD⁺-dependent isomerization of glucose-6-phosphate (G6P) into inositol-1-phosphate (IMP), controlling the rate-limiting step of the inositol pathway. Previous structural studies focused on the detailed molecular mechanism, neglecting large-scale conformational changes that drive the function of this 240 kDa homotetrameric complex. In this study, we identified the active, endogenous MIPS in cell extracts from the thermophilic fungus Thermochaetoides thermophila. By resolving the native structure at 2.48 Å (FSC = 0.143), we revealed a fully populated active site. Utilizing 3D variability analysis, we uncovered conformational states of MIPS, enabling us to directly visualize an order-to-disorder transition at its cataly

SUBMITTER: Trager TK 

PROVIDER: S-EPMC11348189 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature