1hkc
RECOMBINANT HUMAN HEXOKINASE TYPE I COMPLEXED WITH GLUCOSE AND PHOSPHATE
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OverviewOverview
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.
DiseaseDisease
Known disease associated with this structure: Hemolytic anemia due to hexokinase deficiency OMIM:[142600]
About this StructureAbout 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.
ReferenceReference
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
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