1U0G

Crystal structure of mouse phosphoglucose isomerase in complex with erythrose 4-phosphate

Summary for 1U0G

• Entry DOI: 10.2210/pdb1u0g/pdb
• Related: 1U0E 1U0F
• Descriptor: Glucose-6-phosphate isomerase, SULFATE ION, ERYTHOSE-4-PHOSPHATE, ... (6 entities in total)
• Functional Keywords: aldose-ketose isomerase, dimer, isomerase
• Biological source: Mus musculus (house mouse)
• Cellular location: Cytoplasm: P06745
• Total number of polymer chains: 2
• Total formula weight: 129305.03

Authors

Solomons, J.T.G.,Zimmerly, E.M.,Burns, S.,Krishnamurthy, N.,Swan, M.K.,Krings, S.,Muirhead, H.,Chirgwin, J.,Davies, C. (deposition date: 2004-07-13, release date: 2004-11-02, Last modification date: 2024-04-03)

Primary citation

Graham Solomons, J.T.,Zimmerly, E.M.,Burns, S.,Krishnamurthy, N.,Swan, M.K.,Krings, S.,Muirhead, H.,Chirgwin, J.,Davies, C.
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, 2004

PubMed 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.

PubMed: 15342241
DOI: 10.1016/j.jmb.2004.07.085

Experimental method

X-RAY DIFFRACTION (1.7 Å)