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http://purl.uniprot.org/citations/9493266http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/9493266http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/9493266http://www.w3.org/2000/01/rdf-schema#comment"

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."xsd:string
http://purl.uniprot.org/citations/9493266http://purl.org/dc/terms/identifier"doi:10.1016/s0969-2126(98)00006-9"xsd:string
http://purl.uniprot.org/citations/9493266http://purl.org/dc/terms/identifier"doi:10.1016/s0969-2126(98)00006-9"xsd:string
http://purl.uniprot.org/citations/9493266http://purl.uniprot.org/core/author"Aleshin A.E."xsd:string
http://purl.uniprot.org/citations/9493266http://purl.uniprot.org/core/author"Aleshin A.E."xsd:string
http://purl.uniprot.org/citations/9493266http://purl.uniprot.org/core/author"Zeng C."xsd:string
http://purl.uniprot.org/citations/9493266http://purl.uniprot.org/core/author"Zeng C."xsd:string
http://purl.uniprot.org/citations/9493266http://purl.uniprot.org/core/author"Bartunik H.D."xsd:string
http://purl.uniprot.org/citations/9493266http://purl.uniprot.org/core/author"Bartunik H.D."xsd:string
http://purl.uniprot.org/citations/9493266http://purl.uniprot.org/core/author"Bourenkov G.P."xsd:string
http://purl.uniprot.org/citations/9493266http://purl.uniprot.org/core/author"Bourenkov G.P."xsd:string
http://purl.uniprot.org/citations/9493266http://purl.uniprot.org/core/author"Honzatko R.B."xsd:string
http://purl.uniprot.org/citations/9493266http://purl.uniprot.org/core/author"Honzatko R.B."xsd:string
http://purl.uniprot.org/citations/9493266http://purl.uniprot.org/core/author"Fromm H.J."xsd:string
http://purl.uniprot.org/citations/9493266http://purl.uniprot.org/core/author"Fromm H.J."xsd:string
http://purl.uniprot.org/citations/9493266http://purl.uniprot.org/core/date"1998"xsd:gYear
http://purl.uniprot.org/citations/9493266http://purl.uniprot.org/core/date"1998"xsd:gYear
http://purl.uniprot.org/citations/9493266http://purl.uniprot.org/core/name"Structure"xsd:string
http://purl.uniprot.org/citations/9493266http://purl.uniprot.org/core/name"Structure"xsd:string
http://purl.uniprot.org/citations/9493266http://purl.uniprot.org/core/pages"39-50"xsd:string
http://purl.uniprot.org/citations/9493266http://purl.uniprot.org/core/pages"39-50"xsd:string
http://purl.uniprot.org/citations/9493266http://purl.uniprot.org/core/title"The mechanism of regulation of hexokinase: new insights from the crystal structure of recombinant human brain hexokinase complexed with glucose and glucose-6-phosphate."xsd:string
http://purl.uniprot.org/citations/9493266http://purl.uniprot.org/core/title"The mechanism of regulation of hexokinase: new insights from the crystal structure of recombinant human brain hexokinase complexed with glucose and glucose-6-phosphate."xsd:string
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