1hkc

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1hkc, resolution 2.80Å ()
Ligands: , ,
Activity: Hexokinase, with EC number 2.7.1.1
Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml


Contents

RECOMBINANT HUMAN HEXOKINASE TYPE I COMPLEXED WITH GLUCOSE AND PHOSPHATE

Publication Abstract from PubMed

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.

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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Disease

[HXK1_HUMAN] Defects in HK1 are the cause of hexokinase deficiency (HK deficiency) [MIM:235700]. HK deficiency is a rare autosomal recessive disease with nonspherocytic hemolytic anemia as the predominant clinical feature.

About this Structure

1hkc is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

See Also

Reference

  • Aleshin AE, Zeng C, Bartunik HD, Fromm HJ, Honzatko RB. Regulation of hexokinase I: crystal structure of recombinant human brain hexokinase complexed with glucose and phosphate. J Mol Biol. 1998 Sep 18;282(2):345-57. PMID:9735292 doi:10.1006/jmbi.1998.2017

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