Phosphoglucose Isomerase
To represent intramolecular oxidoreductases the interconvert aldoses and ketoses Phosphoglucose isomerase (PGI) was chosen. Phosphoglucose isomerse catalyzes the conversion of glucose-6-phsophate to frustose-6-phosphate in glycolysis and visa versa in gluconeogenisis. As well as catalyzing that reaction, phosphoglucose isomerse is also used in signal transduction pathways as neuroleukin, autocrine motility factor and maturation factor, and therefore is important in tumor growth studies. The serum of PGI can be measured and used as a tumor marker in cancer patient diagnosis and treatment. A deficiency of PGI can cause nonspherocytic hemolytic disease.
PGI has an alpha/beta motif with two globular domains, a large and small, and a C-terminal tail, as well as an interface between the two subunits. The active form of PGI is a dimer with the binding site located in a cleft of the large domain. The structure of PGI is similar to TIM having alpha helicies on the outside with beta-strands in the middle however the number of beta strands is different and the active site is located in a different spot.
Hydrogen bonds form between the active site and substrate upon substrate binding providing stability. Lys420 residue opens the phosphoglucopyranose ring by acting as a base. Then His306 residue extracts a proton from carbon 2 while Glu285 residue donates a proton to C1 carbonyl oxygen. The Glu285 and His306 reverse their roles as acid and bse in the reverse of this reaction. C2 then binds to the hydroxyl group of the phosphate and isomerization is complete. Arg202 stablizes the partial charge on Glu285 and is thought to lock the substrate in a favorable position as well as contributing to the interactions of the phosphate group. Glu145 is implicated in the stability of a partial charge on His306.