کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1941866 | 1536906 | 2015 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: A novel binding of GTP stabilizes the structure and modulates the activities of human phosphoglucose isomerase/autocrine motility factor A novel binding of GTP stabilizes the structure and modulates the activities of human phosphoglucose isomerase/autocrine motility factor](/preview/png/1941866.png)
• GTP competitively inhibits the reaction catalyzed by human phosphoglucose isomerase.
• GTP attenuates the cell migration-stimulating function of phosphoglucose isomerase.
• GTP binding may interfere with the access of substrates to the catalytic site of PGI.
Phosphoglucose isomerase (PGI) catalyzes the interconversion between glucose 6-phosphate and fructose 6-phosphate in the glycolysis pathway. In mammals, the enzyme is also identical to the extracellular proteins neuroleukin, tumor-secreted autocrine motility factor (AMF) and differentiation and maturation mediator for myeloid leukemia. Hereditary deficiency of the enzyme causes non-spherocytic hemolytic anemia in human. In the present study, a novel interaction between GTP and human PGI was corroborated by UV-induced crosslinking, affinity purification and kinetic study. GTP not only inhibits the isomerization activity but also compromises the AMF function of the enzyme. Kinetic studies, including the Yonetani-Theorell method, suggest that GTP is a competitive inhibitor with a Ki value of 63 μM and the GTP-binding site partially overlaps with the catalytic site. In addition, GTP stabilizes the structure of human PGI against heat- and detergent-induced denaturation. Molecular modelling and dynamic simulation suggest that GTP is bound in a syn-conformation with the γ-phosphate group located near the phosphate-binding loop and the ribose moiety positioned away from the active-site residues.
Journal: Biochemistry and Biophysics Reports - Volume 2, July 2015, Pages 14–22