SUNY at Albany
June 19-23, 2001
Structure And Function Of A Protein Moonlighting As Phosphoglucose Isomerase/Autocrine Motility Factor/Neuroleukin
Phosphoglucose isomerase (PGI) plays a central role in both the glycolysis and the gluconeogenesis pathways. PGI has been found to serve functions equivalent to those of autocrine motility factor (AMF), a tumor-secreted cytokine which stimulates cell migration in vitro and metastasis in vivo, and to those of neuroleukin (NLK), a neurotrophic factor for spinal and sensory neurons. We previously reported the substrate-free structure of PGI/AMF/NLK and confirmed that PGI can function as AMF and NLK. Nonetheless, the nature of the substrate active site or the receptor binding site of PGI/AMF/NLK remains poorly understood. In this report, we tested the inhibitory effect of two carbohydrates containing phosphate, 5-phospho-D-arabinonate (5PA) and N-bromoacetylethanolamine phosphate (BAP), on the PGI enzymatic activity and the AMF-induced cell motility. 5PA is a transition state analogue of PGI and BAP is characterized as an active site directed inhibitor of human and rabbit PGI. The results indicate that the substrate and the receptor binding sites of PGI/AMF are located approximate to each other. We also present the crystal structures of PGI complexed with 5-phospho-D-arabinonate (5PA) and N-bromoacetylethanolamine phosphate (BAP) at 2.5 Å and 2.3 Å resolution, respectively.
Chwan-Deng Hsiao (1), Yuh-Ju Sun (1), Chia-Cheng Chou (1), and Menghsiao Meng (2)
Institute of Molecular Biology (1), Academia Sinica, Taipei, Taiwan.