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A novel binding of GTP stabilizes the structure and modulates the activities of human phosphoglucose isomerase/autocrine motility factor
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 matu...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5668625/ https://www.ncbi.nlm.nih.gov/pubmed/29124141 http://dx.doi.org/10.1016/j.bbrep.2015.04.003 |
Sumario: | 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 K(i) 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. |
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