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1hkc
From Proteopedia
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RECOMBINANT HUMAN HEXOKINASE TYPE I COMPLEXED WITH GLUCOSE AND PHOSPHATE
Contents |
Overview
Hexokinase I, the pacemaker of glycolysis in brain tissue and red blood cells, is comprised of two similar domains fused into a single polypeptide chain. The C-terminal half of hexokinase I is catalytically active, whereas the N-terminal half is necessary for the relief of product inhibition by phosphate. A crystalline complex of recombinant human hexokinase I with glucose and phosphate (2.8 A resolution) reveals a single binding site for phosphate and glucose at the N-terminal half of the enzyme. Glucose and phosphate stabilize the N-terminal half in a closed conformation. Unexpectedly, glucose binds weakly to the C-terminal half of the enzyme and does not by itself stabilize a closed conformation. Evidently a stable, closed C-terminal half requires either ATP or glucose 6-phosphate along with glucose. The crystal structure here, in conjunction with other studies in crystallography and directed mutation, puts the phosphate regulatory site at the N-terminal half, the site of potent product inhibition at the C-terminal half, and a secondary site for the weak interaction of glucose 6-phosphate at the N-terminal half of the enzyme. The relevance of crystal structures of hexokinase I to the properties of monomeric hexokinase I and oligomers of hexokinase I bound to the surface of mitochondria is discussed.
Disease
Known disease associated with this structure: Hemolytic anemia due to hexokinase deficiency OMIM:[142600]
About this Structure
1HKC 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
Regulation of hexokinase I: crystal structure of recombinant human brain hexokinase complexed with glucose and phosphate., Aleshin AE, Zeng C, Bartunik HD, Fromm HJ, Honzatko RB, J Mol Biol. 1998 Sep 18;282(2):345-57. PMID:9735292
Page seeded by OCA on Thu Feb 21 13:02:11 2008
Categories: Hexokinase | Homo sapiens | Single protein | Aleshin, A E. | Honzatko, R B. | GLC | K | PO4 | Allosteric enzyme | Glucose | Glycolysis | Phosphate | Phosphotransferase
