Glucose 6-phosphate release of wild-type and mutant human brain hexokinases from mitochondria

ASIAIR > College of Medical and Health Science > Department of Food Nutrition and Healthy Biotechnology > Journal Article > Item 310904400/7835

Please use this identifier to cite or link to this item: http://asiair.asia.edu.tw/ir/handle/310904400/7835

Title:	Glucose 6-phosphate release of wild-type and mutant human brain hexokinases from mitochondria
Authors:	Skaff, D.Andrew;Kim, Chang Sup;Henry J Tsai;Richard B Honzatko;Herbert J Fromm
Date:	2005
Issue Date:	2010-02-26
Publisher:	Asia University
Abstract:	One molecule of glucose 6-phosphate inhibits brain hexokinase (HKI) with high affinity by binding to either one of two sites located in distinct halves of the enzyme. In addition to potent inhibition, glucose 6-phosphate releases HKI from the outer leaflet of mitochondria; however, the site of glucose 6-phosphate association responsible for the release of HKI is unclear. The incorporation of a C-terminal polyhistidine tag on HKI facilitates the rapid purification of recombinant enzyme from Escherichia coli. The tagged construct has N-formyl methionine as its first residue and has mitochondrial association properties comparable with native brain hexokinases. Release of wild-type and mutant hexokinases from mitochondria by glucose 6-phosphate follow equilibrium models, which explain the release phenomenon as the repartitioning of ligand-bound HKI between solution and the membrane. Mutations that block the binding of glucose 6-phosphate to the C-terminal half of HKI have little or no effect on the glucose 6-phosphate release. In contrast, mutations that block glucose 6-phosphate binding to the N-terminal half require ∼7-fold higher concentrations of glucose 6-phosphate for the release of HKI. Results here implicate a primary role for the glucose 6-phosphate binding site at the N-terminal half of HKI in the release mechanism.
Relation:	The Journal of Biological Chemistry, 280(46):38403-38409.
Appears in Collections:	[食品營養與保健生技學系] 期刊論文

Files in This Item:

File	Description	Size	Format
		0Kb	Unknown	480	View/Open
310904400-7835 .doc		30Kb	Microsoft Word	306	View/Open

Loading...