The crystal structure of phosphoglucose isomerase/autocrine motility factor/neuroleukin complexed with its carbohydrate phosphate inhibitors suggestsits substrate/receptor recognition

Phosphoglucose isomerase catalyzes the reversible isomerization of glucose 6-phosphate to fructose B-phosphate. In addition, phosphoglucose isomerase has been shown to have functions equivalent to neuroleukin, autocrine motil ity factor, and maturation factor. Here we present the crystal structures o f phosphoglucose isomerase complexed with 5-phospho-D-arabinonate and N-bro moacetylethanolamine phosphate at 2.5- and 2.3-Angstrom resolution, respect ively. The inhibitors bind to a region within the domains' interface and in teract with a histidine residue (His(306)) from the other subunit. We also demonstrated that the inhibitors not only affect the enzymatic activity of phosphoglucose isomerase, but can also inhibit the autocrine motility facto r-induced cell motility of CT-26 mouse colon tumor cells. These results ind icate that the substrate and the receptor binding sites of phosphoglucose i somerase and autocrine motility factor are located within close proximity t o each other. Based on these two complex structures, together with biologic al and biochemical results, we propose a possible isomerization mechanism f or phosphoglucose isomerase.