The crystal structure of human phosphoglucose isomerase at 1.6 A resolution: implications for catalytic mechanism, cytokine activity and haemolytic anaemia.
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Read J, Pearce J, Li X, Muirhead H, Chirgwin J, Davies C
The crystal structure of human phosphoglucose isomerase at 1.6 A resolution: implications for catalytic mechanism, cytokine activity and haemolytic anaemia.
J Mol Biol. 2001 Jun 1;309(2):447-63.
- PubMed ID
- 11371164 [ View in PubMed]
- Abstract
Phosphoglucose isomerase (PGI) is a multifunctional protein, which, inside the cell, functions as a housekeeping enzyme of glycolysis and gluconeogenesis and, outside the cell, exerts wholly unrelated cytokine properties. We have determined the structure of human PGI to a resolution of 1.6 A using X-ray crystallography. The structure is highly similar to other PGIs, especially the architecture of the active site. Fortuitous binding of a sulphate molecule from the crystallisation solution has facilitated an accurate description of the substrate phosphate-binding site. Comparison with both native and inhibitor-bound rabbit PGI structures shows that two loops move closer to the active site upon binding inhibitor. Interestingly, the human structure most closely resembles the inhibitor-bound structure, suggesting that binding of the phosphate moiety of the substrate may trigger this conformational change. We suggest a new mechanism for catalysis that uses Glu357 as the base catalyst for the isomerase reaction rather than His388 as proposed previously. The human PGI structure has also provided a detailed framework with which to map mutations associated with non-spherocytic haemolytic anaemia.