1P1J

Crystal structure of the 1L-myo-inositol 1-phosphate synthase complexed with NADH

Summary for 1P1J

• Entry DOI: 10.2210/pdb1p1j/pdb
• Related: 1P1F 1P1H 1P1I 1P1K
• Descriptor: Inositol-3-phosphate synthase, PHOSPHATE ION, 1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE, ... (5 entities in total)
• Functional Keywords: 1l-myo-inositol 1-phosphate, nadh, isomerase, rossmann fold
• Biological source: Saccharomyces cerevisiae (baker's yeast)
• Cellular location: Cytoplasm: P11986
• Total number of polymer chains: 2
• Total formula weight: 121120.54

Authors

Jin, X.,Geiger, J.H. (deposition date: 2003-04-12, release date: 2003-07-08, Last modification date: 2024-02-14)

Primary citation

Jin, X.,Geiger, J.H.
Structures of NAD(+)- and NADH-bound 1-l-myo-inositol 1-phosphate synthase.
Acta Crystallogr.,Sect.D, 59:1154-1164, 2003

PubMed Abstract: 1-l-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, an intramolecular aldol cyclization and a reduction. Here, the structure of the enzyme in its NAD(+)-bound, NADH-bound and apo forms is presented. These structures confirm that a significant portion of the active site is disordered in the absence of a small molecule, as none of the NAD(+)-bound forms of the enzyme have ordered active sites. On the other hand, the NADH-bound form contains two small molecules in the active site: a phosphate and glycerol. The entire active site is ordered in the presence of these two molecules, completely encapsulating them within the interior cavity. Significant changes in the structure of the active site are also seen, including repositioning of the nicotinamide ring and a motion of a loop region to accommodate the bound phosphate. These changes call into question the mechanism previously proposed for the enzyme. A comparison of the yeast and mycobacterial enzymes shows a surprisingly large change in the relative orientation of the catalytic and Rossmann-fold domains in the two enzymes.

PubMed: 12832758
DOI: 10.1107/S0907444903008205

Experimental method

X-RAY DIFFRACTION (1.7 Å)