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Papers In Press, published online ahead of print January 4, 2002
Department of Chemistry, Michigan State University, East Lansing, MI 48824
Corresponding Author: geiger{at}cem.msu.edu
1L-myo-inositol-1-phosphate synthase catalyzes the conversion of D-glucose 6-phosphate to 1-L-myo-inositol-1-phosphate, the first and rate limiting step in the biosynthesis of all inositol-containing compounds. It involves an oxidation, intramolecular aldol cyclization and reduction. We have determined the crystal structure of MIP synthase bound to NAD and bound to an inhibitor, 2-deoxy-glucitol-6-phosphate. While 58 amino acids are disordered in the unbound form of the enzyme in the vicinity of the active site, the inhibitor nucleates the folding of this domain in a striking example of induced fit, serving to completely encapsulate it within the enzyme. Three helices and a long beta strand are formed in this process. We postulate a mechanism for the conversion based on the structure of the inhibitor-bound complex.
J. Biol. Chem, 10.1074/jbc.M109371200
Submitted on September 27, 2001
Revised on January 2, 2002
Accepted on January 4, 2002
The crystal structure and mechanism of 1L-myo-Inositol-1-phosphate synthase
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