PDBsum entry: 1u0f

Isomerase

PDB id: 1u0f

Contents

Protein chains

556 a.a. *

Ligands

G6P-G6Q

SO4 ×8

GOL ×12

BME

Waters ×858

* Residue conservation analysis

PDB id:

1u0f

Name:

Isomerase

Title:

Crystal structure of mouse phosphoglucose isomerase in compl glucose 6-phosphate

Structure:

Glucose-6-phosphate isomerase. Chain: a, b. Synonym: gpi, phosphoglucose isomerase, pgi, phosphohexose phi, neuroleukin, nlk. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Gene: gpi. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

1.60Å R-factor: 0.180 R-free: 0.207

Authors:

J.T.G.Solomons,E.M.Zimmerly,S.Burns,N.Krishnamurthy,M.K.Swan S.Krings,H.Muirhead,J.Chirgwin,C.Davies

Key ref:

J.T.Graham Solomons et al. (2004). The crystal structure of mouse phosphoglucose isomerase at 1.6A resolution and its complex with glucose 6-phosphate reveals the catalytic mechanism of sugar ring opening. J Mol Biol, 342, 847-860. PubMed id: 15342241 DOI: 10.1016/j.jmb.2004.07.085

Date:

13-Jul-04 Release date: 02-Nov-04

Protein chains

P06745  (G6PI_MOUSE) -  Glucose-6-phosphate isomerase

Seq: 558 a.a.

Struc: 556 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.5.3.1.9 - Glucose-6-phosphate isomerase.
• Reaction: D-glucose 6-phosphate = D-fructose 6-phosphate

D-glucose 6-phosphate (Bound ligand (Het Group name = G6P) corresponds exactly) = D-fructose 6-phosphate

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

 Gene Ontology (GO) functional annotation 

• Cellular component: extracellular region (3 terms)
• Biological process: angiogenesis (4 terms)
• Biochemical function: protein binding (5 terms)

Added reference

DOI no: 10.1016/j.jmb.2004.07.085

J Mol Biol 342:847-860 (2004)

PubMed id: 15342241

The crystal structure of mouse phosphoglucose isomerase at 1.6A resolution and its complex with glucose 6-phosphate reveals the catalytic mechanism of sugar ring opening.

J.T.Graham Solomons, E.M.Zimmerly, S.Burns, N.Krishnamurthy, M.K.Swan, S.Krings, H.Muirhead, J.Chirgwin, C.Davies.

ABSTRACT

Phosphoglucose isomerase (PGI) is an enzyme of glycolysis that interconverts glucose 6-phosphate (G6P) and fructose 6-phosphate (F6P) but, outside the cell, is a multifunctional cytokine. High-resolution crystal structures of the enzyme from mouse have been determined in native form and in complex with the inhibitor erythrose 4-phosphate, and with the substrate glucose 6-phosphate. In the substrate-bound structure, the glucose sugar is observed in both straight-chain and ring forms. This structure supports a specific role for Lys518 in enzyme-catalyzed ring opening and we present a "push-pull" mechanism in which His388 breaks the O5-C1 bond by donating a proton to the ring oxygen atom and, simultaneously, Lys518 abstracts a proton from the C1 hydroxyl group. The reverse occurs in ring closure. The transition from ring form to straight-chain substrate is achieved through rotation of the C3-C4 bond, which brings the C1-C2 region into close proximity to Glu357, the base catalyst for the isomerization step. The structure with G6P also explains the specificity of PGI for glucose 6-phosphate over mannose 6-isomerase (M6P). To isomerize M6P to F6P requires a rotation of its C2-C3 bond but in PGI this is sterically blocked by Gln511.

Selected figure(s)

Figure 3.
Figure 3. The structure of mouse PGI in complex with glucose 6-phosphate at 1.6 Å resolution. (a) A stereo picture of the active site region of molecule A, showing unbiased |F[o]| -|F[c]| electron density corresponding to G6P, contoured at 1 s and coloured blue. The ring form of G6P is shown as cyan bonds and that of the straight chain as green bonds. Water molecules are represented as red spheres and potential hydrogen bonds are shown as broken lines. The proximity of Glu357 to carbon atoms 1 and 2 of G6P is denoted by broken lines. This Figure was prepared using Pymol (http://pymol.sourceforge.net/). (b) The contacts between PGI and the ring form of G6P. The distance between specific atoms are shown as broken lines and the distances are in Å. (c) Contacts between PGI and the straight-chain form of G6P.

Figure 5.
Figure 5. A comprehensive reaction mechanism for phosphoglucose isomerase. This scheme illustrates the critical role of Lys518 in ring opening and ring closing, as well as the rotation about the C3-C4 bond of the substrate that is required to bring C1-C2 (the site of proton transfer) alongside the base catalyst, Glu357. See the text for details.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2004, 342, 847-860) copyright 2004.

Figures were selected by an automated process.