Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/50350
標題: Effects of inherited mutations on catalytic activity and structural stability of human glucose-6-phosphate isomerase expressed in Escherichia coli
作者: Lin, H.Y.
孟孟孝
Kao, Y.H.
Chen, S.T.
Meng, M.
關鍵字: Glucose-6-phosphate isomerase;Phosphoglucose isomerase;Nonspherocytic;hemolytic anemia;HNSHA;Blue native PAGE;Thermostability;autocrine motility factor;human phosphoglucose isomerase;chronic;hemolytic-anemia;1.6 angstrom resolution;crystal-structure;phosphohexose isomerase;gpi deficiency;rheumatoid-arthritis;phosphate;enzyme
Project: Biochimica Et Biophysica Acta-Proteins and Proteomics
期刊/報告no:: Biochimica Et Biophysica Acta-Proteins and Proteomics, Volume 1794, Issue 2, Page(s) 315-323.
摘要: 
Glucose-6-phosphate isomerase (GPI), a homodimeric enzyme, catalyzes the interconversion between glucose-6-phosphate and fructose-6-phosphate. In mammals, it can also act as an autocrine motility factor, neuroleukin, and maturation factor. Deficiency of the enzymatic activity in red blood cells causes nonspherocytic hemolytic anemia in human. To gain a more complete understanding of the molecular basis for the hemolytic anemia due to the GPI-deficiency. the wild-type enzyme and sixteen genetic variants were expressed in Escherichia coli and functionally characterized. Conclusions are as follows: (1) mutations usually have negative influences on catalytic parameters, particularly k(cat), as well as structure stability; (2) mutations at or close to the active site, including R273H, H389R, and 52781, cause great damage to the catalytic function, yet those at distance can still reduce the magnitude of kcat, despite lesser extents; (3) mutations decrease the enzyme tolerance to heat or SDS by mechanisms of decreasing packing efficiency (V101M, T1951, S278L L487F, L339P, T375R, 1525T), weakening network bonding (R75G, R347C, R347H, R472H, E495K), increasing water-accessible hydrophobic surface (R83W), and destabilizing the ternary structure (T1951, R347C, R347H, and 1525T); (4) A300P, L339P, and E495K mutations may also negatively affect the protein folding efficiency. (C) 2008 Elsevier B.V. All rights reserved.
URI: http://hdl.handle.net/11455/50350
ISSN: 1570-9639
DOI: 10.1016/j.bbapap.2008.11.004
Appears in Collections:生物科技學研究所

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