1HKC

Regulation of hexokinase I: crystal structure of recombinant human brain hexokinase complexed with glucose and phosphate.

(1998) J Mol Biol 282: 345-357

• PubMed: 9735292 Search on PubMed
• DOI: https://doi.org/10.1006/jmbi.1998.2017
• Primary Citation of Related Structures:  
  1HKC


• PubMed Abstract: 
  

  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.

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Organizational Affiliation: 

Department of Biochemistry and Biophysics, Iowa State University, Ames, IA 50011, USA.