The Structure and Mechanism of myo-Inositol-1-Phosphate Synthase
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The first and rate-limiting step in the biosynthesis of myo-inositol is the conversion of D-glucose 6-phosphate to 1L-myo-inositol 1-phosphate catalyzed by 1L-myo-inositol 1-phosphate synthase (MIP synthase). MIP synthase has been identified in a wide variety of organisms from bacteria to humans and is relatively well-conserved throughout evolution. It is probably homotetrameric in most if not all cases and always requires NAD+ as a cofactor, with NADH being reconverted to NAD+ in the catalytic cycle. This review focuses on the structure and mechanism of MIP synthase, with a particular emphasis on the mechanistic insights that have come from several recent structures of the enzyme. These include the structure of the enzyme from Saccharomyces cerevisiae, Archeoglobus fulgidus and Mycobacterium tuberculosis.
KeywordsInositol biosynthesis 1L-myo-inositol 1-phosphate synthase D-glucose 6-phosphate enzyme structure enzyme mechanism
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