PDBsum entry 1jkf

Isomerase

PDB id: 1jkf

Contents

Protein chains

466 a.a. *

Ligands

NAD ×2

Waters ×538

* Residue conservation analysis

PDB id:

1jkf

Name:

Isomerase

Title:

Holo 1l-myo-inositol-1-phosphate synthase

Structure:

Myo-inositol-1-phosphate synthase. Chain: a, b. Engineered: yes

Source:

Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Dimer (from PDB file)

Resolution:

2.40Å R-factor: 0.205 R-free: 0.243

Authors:

A.J.Stein,J.H.Geiger

Key ref:

A.J.Stein and J.H.Geiger (2002). The crystal structure and mechanism of 1-L-myo-inositol- 1-phosphate synthase. J Biol Chem, 277, 9484-9491. PubMed id: 11779862 DOI: 10.1074/jbc.M109371200

Date:

12-Jul-01 Release date: 10-Apr-02

Protein chains

P11986  (INO1_YEAST) -  Inositol-3-phosphate synthase from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 533 a.a.

Struc: 466 a.a.

Enzyme reactions

• Enzyme class: E.C.5.5.1.4 - inositol-3-phosphate synthase.
• Pathway: myo-Inositol Biosynthesis
• Reaction: D-glucose 6-phosphate = 1D-myo-inositol 3-phosphate
• Cofactor: NAD(+)

NAD(+) (Bound ligand (Het Group name = NAD) corresponds exactly)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1074/jbc.M109371200

J Biol Chem 277:9484-9491 (2002)

PubMed id: 11779862

The crystal structure and mechanism of 1-L-myo-inositol- 1-phosphate synthase.

A.J.Stein, J.H.Geiger.

ABSTRACT

1-l-myo-Inositol-1-phosphate synthase catalyzes the conversion of d-glucose 6-phosphate to 1-l-myo-inositol-1-phosphate (MIP), 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 first crystal structure of MIP synthase. We present structures of both the NAD-bound enzyme and the enzyme 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.

Selected figure(s)

Figure 2.
Fig. 2. Ribbon model of the MIP synthase tetramer in the absence of inhibitor. This and all other structure figures were made using the program RIBBONS (55). The top two monomers are colored red and blue, make up one asymmetric unit, and are related by a noncrystallographic 2-fold axis that is roughly in the plane of the page. The bottom two monomers are green and are related to the top two monomers by a crystallographic 2-fold axis running roughly perpendicular to the page.

Figure 6.
Fig. 6. Proposed mechanism for the transformation catalyzed by MIP synthase.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 9484-9491) copyright 2002.

Figures were selected by an automated process.