InterPro: IPR018189 Phosphoglucose isomerase, conserved site

Phosphoglucose isomerase (EC:5.3.1.9) (PGI) [1, 2] is a dimeric enzyme that catalyses the reversible isomerization of glucose-6-phosphate and fructose-6-phosphate. PGI is involved in different pathways: in most higher organisms it is involved in glycolysis; in mammals it is involved in gluconeogenesis; in plants in carbohydrate biosynthesis; in some bacteria it provides a gateway for fructose into the Entner-Doudouroff pathway. The multifunctional protein, PGI, is also known as neuroleukin (a neurotrophic factor that mediates the differentiation of neurons), autocrine motility factor (a tumour-secreted cytokine that regulates cell motility), differentiation and maturation mediator and myofibril-bound serine proteinase inhibitor, and has different roles inside and outside the cell. In the cytoplasm, it catalyses the second step in glycolysis, while outside the cell it serves as a nerve growth factor and cytokine [3].

PGI from Bacillus stearothermophilus has an open twisted alpha/beta structural motif consisting of two globular domains and two protruding parts. It has been suggested that the top part of the large domain together with one of the protruding loops might participate in inducing the neurotrophic activity [4]. The structure of rabbit muscle phosphoglucose isomerase complexed with various inhibitors shows that the enzyme is a dimer with two alpha/beta-sandwich domains in each subunit. The location of the bound D-gluconate 6-phosphate inhibitor leads to the identification of residues involved in substrate specificity. In addition, the positions of amino acid residues that are substituted in the genetic disease nonspherocytic hemolytic anemia suggest how these substitutions can result in altered catalysis or protein stability [3, 5].