Sun Y J, Chou C C, Chen W S, Wu R T, Meng M, Hsiao C D
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan 11529, Republic of China.
Proc Natl Acad Sci U S A. 1999 May 11;96(10):5412-7. doi: 10.1073/pnas.96.10.5412.
Phosphoglucose isomerase (PGI) plays a central role in both the glycolysis and the gluconeogenesis pathways. We present here the complete crystal structure of PGI from Bacillus stearothermophilus at 2.3-A resolution. We show that PGI has cell-motility-stimulating activity on mouse colon cancer 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 alpha/beta structural motif consisting of two globular domains and two protruding parts. Based on this substrate-free structure, together with the previously published biological, biochemical, and modeling results, we postulate a possible substrate-binding site that is located within the domains' interface for PGI and AMF. In addition, the structure provides evidence suggesting that the top part of the large domain together with one of the protruding loops might participate in inducing the neurotrophic activity.
磷酸葡萄糖异构酶(PGI)在糖酵解和糖异生途径中都起着核心作用。我们在此展示嗜热脂肪芽孢杆菌PGI在2.3埃分辨率下的完整晶体结构。我们发现PGI对小鼠结肠癌细胞具有细胞运动刺激活性,类似于内源性自分泌运动因子(AMF)。PGI还能增强神经元祖细胞上的神经突生长,类似于神经白细胞素的作用。结果证实PGI就是神经白细胞素和AMF。PGI具有一种开放的扭曲α/β结构基序,由两个球状结构域和两个突出部分组成。基于这种无底物结构,结合先前发表的生物学、生物化学和建模结果,我们推测了一个可能位于PGI和AMF结构域界面内的底物结合位点。此外,该结构提供了证据表明大结构域的顶部与其中一个突出环可能参与诱导神经营养活性。