1iat
CRYSTAL STRUCTURE OF HUMAN PHOSPHOGLUCOSE ISOMERASE/NEUROLEUKIN/AUTOCRINE MOTILITY FACTOR/MATURATION FACTOR
OverviewOverview
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.
DiseaseDisease
Known disease associated with this structure: Hemolytic anemia due to glucosephosphate isomerase deficiency OMIM:[172400], Hydrops fetalis, one form OMIM:[172400]
About this StructureAbout this Structure
1IAT is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
The crystal structure of human phosphoglucose isomerase at 1.6 A resolution: implications for catalytic mechanism, cytokine activity and haemolytic anaemia., Read J, Pearce J, Li X, Muirhead H, Chirgwin J, Davies C, J Mol Biol. 2001 Jun 1;309(2):447-63. PMID:11371164 Page seeded by OCA on Fri May 2 19:46:59 2008