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Updated: Oct 1, 2026

Preparation of Quality Inositol Pyrophosphates
Published on: September 3, 2011
Crystal structure of inositol 1-phosphate synthase from Mycobacterium tuberculosis, a key enzyme in
Richard A Norman1, Mark S B McAlister, Judith Murray-Rust
1Structural Biology Laboratory, Cancer Research U K, London, United Kingdom.
Abstract:
Phosphatidylinositol (PI) is essential for Mycobacterium tuberculosis viability and the enzymes involved in the PI biosynthetic pathway are potential antimycobacterial agents for which little structural information is available. The rate-limiting step in the pathway is the production of (L)-myo-inositol 1-phosphate from (D)-glucose 6-phosphate, a complex reaction catalyzed by the enzyme inositol 1-phosphate synthase. We have determined the crystal structure of this enzyme from Mycobacterium tuberculosis (tbINO) at 1.95 A resolution, bound to the cofactor NAD+. The active site is located within a deep cleft at the junction between two domains. The unexpected presence of a zinc ion here suggests a mechanistic difference from the eukaryotic inositol synthases, which are stimulated by monovalent cations, that may be exploitable in developing selective inhibitors of tbINO.
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