1hkb
From Proteopedia
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==Overview== | ==Overview== | ||
| - | BACKGROUND: Hexokinase I is the pacemaker of glycolysis in brain tissue. | + | BACKGROUND: Hexokinase I is the pacemaker of glycolysis in brain tissue. The type I isozyme exhibits unique regulatory properties in that physiological levels of phosphate relieve potent inhibition by the product, glucose-6-phosphate (Gluc-6-P). The 100 kDa polypeptide chain of hexokinase I consists of a C-terminal (catalytic) domain and an N-terminal (regulatory) domain. Structures of ligated hexokinase I should provide a basis for understanding mechanisms of catalysis and regulation at an atomic level. RESULTS: The complex of human hexokinase I with glucose and Gluc-6-P (determined to 2.8 A resolution) is a dimer with twofold molecular symmetry. The N- and C-terminal domains of one monomer interact with the C- and N-terminal domains, respectively, of the symmetry-related monomer. The two domains of a monomer are connected by a single alpha helix and each have the fold of yeast hexokinase. Salt links between a possible cation-binding loop of the N-terminal domain and a loop of the C-terminal domain may be important to regulation. Each domain binds single glucose and Gluc-6-P molecules in proximity to each other. The 6-phosphoryl group of bound Gluc-6-P at the C-terminal domain occupies the putative binding site for ATP, whereas the 6-phosphoryl group at the N-terminal domain may overlap the binding site for phosphate. CONCLUSIONS: The binding synergism of glucose and Gluc-6-P probably arises out of the mutual stabilization of a common (glucose-bound) conformation of hexokinase I. Conformational changes in the N-terminal domain in response to glucose, phosphate, and/or Gluc-6-P may influence the binding of ATP to the C-terminal domain. |
==Disease== | ==Disease== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Aleshin, A | + | [[Category: Aleshin, A E.]] |
| - | [[Category: Bartunik, H | + | [[Category: Bartunik, H D.]] |
| - | [[Category: Burenkov, G | + | [[Category: Burenkov, G P.]] |
| - | [[Category: Fromm, H | + | [[Category: Fromm, H J.]] |
| - | [[Category: Honzatko, R | + | [[Category: Honzatko, R B.]] |
[[Category: Zeng, C.]] | [[Category: Zeng, C.]] | ||
[[Category: CA]] | [[Category: CA]] | ||
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[[Category: phosphotransferase]] | [[Category: phosphotransferase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:02:08 2008'' |
Revision as of 11:02, 21 February 2008
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CRYSTAL STRUCTURE OF RECOMBINANT HUMAN BRAIN HEXOKINASE TYPE I COMPLEXED WITH GLUCOSE AND GLUCOSE-6-PHOSPHATE
Contents |
Overview
BACKGROUND: Hexokinase I is the pacemaker of glycolysis in brain tissue. The type I isozyme exhibits unique regulatory properties in that physiological levels of phosphate relieve potent inhibition by the product, glucose-6-phosphate (Gluc-6-P). The 100 kDa polypeptide chain of hexokinase I consists of a C-terminal (catalytic) domain and an N-terminal (regulatory) domain. Structures of ligated hexokinase I should provide a basis for understanding mechanisms of catalysis and regulation at an atomic level. RESULTS: The complex of human hexokinase I with glucose and Gluc-6-P (determined to 2.8 A resolution) is a dimer with twofold molecular symmetry. The N- and C-terminal domains of one monomer interact with the C- and N-terminal domains, respectively, of the symmetry-related monomer. The two domains of a monomer are connected by a single alpha helix and each have the fold of yeast hexokinase. Salt links between a possible cation-binding loop of the N-terminal domain and a loop of the C-terminal domain may be important to regulation. Each domain binds single glucose and Gluc-6-P molecules in proximity to each other. The 6-phosphoryl group of bound Gluc-6-P at the C-terminal domain occupies the putative binding site for ATP, whereas the 6-phosphoryl group at the N-terminal domain may overlap the binding site for phosphate. CONCLUSIONS: The binding synergism of glucose and Gluc-6-P probably arises out of the mutual stabilization of a common (glucose-bound) conformation of hexokinase I. Conformational changes in the N-terminal domain in response to glucose, phosphate, and/or Gluc-6-P may influence the binding of ATP to the C-terminal domain.
Disease
Known disease associated with this structure: Hemolytic anemia due to hexokinase deficiency OMIM:[142600]
About this Structure
1HKB is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Hexokinase, with EC number 2.7.1.1 Known structural/functional Sites: , , , , , , , , , , and . Full crystallographic information is available from OCA.
Reference
The mechanism of regulation of hexokinase: new insights from the crystal structure of recombinant human brain hexokinase complexed with glucose and glucose-6-phosphate., Aleshin AE, Zeng C, Bourenkov GP, Bartunik HD, Fromm HJ, Honzatko RB, Structure. 1998 Jan 15;6(1):39-50. PMID:9493266
Page seeded by OCA on Thu Feb 21 13:02:08 2008
Categories: Hexokinase | Homo sapiens | Single protein | Aleshin, A E. | Bartunik, H D. | Burenkov, G P. | Fromm, H J. | Honzatko, R B. | Zeng, C. | CA | G6P | GLC | Allosteric enzyme | Glucose | Glucose-6-phosphate | Glycolysis | Phosphotransferase
