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http://purl.uniprot.org/citations/10574795http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/10574795http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/10574795http://www.w3.org/2000/01/rdf-schema#comment"

Background

Hexokinase I sets the pace of glycolysis in the brain, catalyzing the ATP-dependent phosphorylation of glucose. The catalytic properties of hexokinase I are dependent on product inhibition as well as on the action of phosphate. In vivo, a large fraction of hexokinase I is bound to the mitochondrial outer membrane, where the enzyme adopts a tetrameric assembly. The mitochondrion-bound hexokinase I is believed to optimize the ATP/ADP exchange between glucose phosphorylation and the mitochondrial oxidative phosphorylation reactions.

Results

The crystal structure of human hexokinase I has been determined at 2.25 A resolution. The overall structure of the enzyme is in keeping with the closed conformation previously observed in yeast hexokinase. One molecule of the ATP analogue AMP-PNP is bound to each N-terminal domain of the dimeric enzyme in a surface cleft, showing specific interactions with the nucleotide, and localized positive electrostatic potential. The molecular symmetry brings the two bound AMP-PNP molecules, at the centre of two extended surface regions, to a common side of the dimeric hexokinase I molecule.

Conclusions

The binding of AMP-PNP to a protein site separated from the catalytic centre of human hexokinase I can be related to the role played by some nucleotides in dissociating the enzyme from the mitochondrial membrane, and helps in defining the molecular regions of hexokinase I that are expected to be in contact with the mitochondrion. The structural information presented here is in keeping with monoclonal antibody mapping of the free and mitochondrion-bound forms of the enzyme, and with sequence analysis of hexokinases that differ in their mitochondria binding properties."xsd:string
http://purl.uniprot.org/citations/10574795http://purl.org/dc/terms/identifier"doi:10.1016/s0969-2126(00)80032-5"xsd:string
http://purl.uniprot.org/citations/10574795http://purl.org/dc/terms/identifier"doi:10.1016/s0969-2126(00)80032-5"xsd:string
http://purl.uniprot.org/citations/10574795http://purl.uniprot.org/core/author"Bolognesi M."xsd:string
http://purl.uniprot.org/citations/10574795http://purl.uniprot.org/core/author"Bolognesi M."xsd:string
http://purl.uniprot.org/citations/10574795http://purl.uniprot.org/core/author"Rosano C."xsd:string
http://purl.uniprot.org/citations/10574795http://purl.uniprot.org/core/author"Rosano C."xsd:string
http://purl.uniprot.org/citations/10574795http://purl.uniprot.org/core/author"Rizzi M."xsd:string
http://purl.uniprot.org/citations/10574795http://purl.uniprot.org/core/author"Rizzi M."xsd:string
http://purl.uniprot.org/citations/10574795http://purl.uniprot.org/core/author"Murshudov G."xsd:string
http://purl.uniprot.org/citations/10574795http://purl.uniprot.org/core/author"Murshudov G."xsd:string
http://purl.uniprot.org/citations/10574795http://purl.uniprot.org/core/author"Bianchi M."xsd:string
http://purl.uniprot.org/citations/10574795http://purl.uniprot.org/core/author"Bianchi M."xsd:string
http://purl.uniprot.org/citations/10574795http://purl.uniprot.org/core/author"Sabini E."xsd:string
http://purl.uniprot.org/citations/10574795http://purl.uniprot.org/core/author"Sabini E."xsd:string
http://purl.uniprot.org/citations/10574795http://purl.uniprot.org/core/author"Magnani M."xsd:string
http://purl.uniprot.org/citations/10574795http://purl.uniprot.org/core/author"Magnani M."xsd:string
http://purl.uniprot.org/citations/10574795http://purl.uniprot.org/core/author"Deriu D."xsd:string
http://purl.uniprot.org/citations/10574795http://purl.uniprot.org/core/author"Deriu D."xsd:string
http://purl.uniprot.org/citations/10574795http://purl.uniprot.org/core/author"Serafini G."xsd:string
http://purl.uniprot.org/citations/10574795http://purl.uniprot.org/core/author"Serafini G."xsd:string
http://purl.uniprot.org/citations/10574795http://purl.uniprot.org/core/date"1999"xsd:gYear
http://purl.uniprot.org/citations/10574795http://purl.uniprot.org/core/date"1999"xsd:gYear
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