The crystal structure of a multifunctional protein: Phosphoglucose isomerase autocrine motility factor neuroleukin

Phosphoglucose isomerase (PGI) plays a central role in both the glycolysis and the gluconeogenesis pathways. We present here the complete crystal stru cture of PGI from Bacillus stearothermophilus at 2.3-Angstrom resolution. W e show that PGI has cell-motility-stimulating activity on mouse colon cance r cells similar to that of endogenous autocrine motility factor (AMF). PGI can also enhance neurite outgrowth on neuronal progenitor cells similar to that observed for neuroleukin. The results confirm that PGI is neuroleukin and AMF. PGI has an open twisted alp structural motif consisting of two glo bular domains and two protruding parts. Based on this substrate-free struct ure, together with the previously published biological, biochemical, and mo deling results, we postulate a possible substrate-binding site that is loca ted within the domains' interface for PGI and AMF. In addition, the structu re provides evidence suggesting that the top part of the large domain toget her with one of the protruding loops might participate in inducing the neur otrophic activity.