PMID- 10574795
OWN - NLM
STAT- MEDLINE
DCOM- 19991214
LR  - 20190915
IS  - 0969-2126 (Print)
IS  - 0969-2126 (Linking)
VI  - 7
IP  - 11
DP  - 1999 Nov 15
TI  - Binding of non-catalytic ATP to human hexokinase I highlights the structural
      components for enzyme-membrane association control.
PG  - 1427-37
AB  - 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.
FAU - Rosano, C
AU  - Rosano C
AD  - Dipartimento di Fisica - INFM, Centro Biotecnologie Avanzate - IST, Universita'
      di Genova, Genova, 10. I-16132, Italy.
FAU - Sabini, E
AU  - Sabini E
FAU - Rizzi, M
AU  - Rizzi M
FAU - Deriu, D
AU  - Deriu D
FAU - Murshudov, G
AU  - Murshudov G
FAU - Bianchi, M
AU  - Bianchi M
FAU - Serafini, G
AU  - Serafini G
FAU - Magnani, M
AU  - Magnani M
FAU - Bolognesi, M
AU  - Bolognesi M
LA  - eng
SI  - PDB/1QHA
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Structure
JT  - Structure (London, England : 1993)
JID - 101087697
RN  - 0 (Recombinant Proteins)
RN  - 56-73-5 (Glucose-6-Phosphate)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Adenosine Triphosphate/*metabolism
MH  - Amino Acid Sequence
MH  - Binding Sites
MH  - Catalysis
MH  - Cell Membrane/enzymology
MH  - Crystallography, X-Ray
MH  - Glucose/metabolism
MH  - Glucose-6-Phosphate/metabolism
MH  - Hexokinase/chemistry/*metabolism
MH  - Humans
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Protein Binding
MH  - Protein Conformation
MH  - Protein Folding
MH  - Recombinant Proteins/chemistry/metabolism
MH  - Sequence Homology, Amino Acid
EDAT- 1999/11/27 00:00
MHDA- 1999/11/27 00:01
CRDT- 1999/11/27 00:00
PHST- 1999/11/27 00:00 [pubmed]
PHST- 1999/11/27 00:01 [medline]
PHST- 1999/11/27 00:00 [entrez]
AID - S0969-2126(00)80032-5 [pii]
AID - 10.1016/s0969-2126(00)80032-5 [doi]
PST - ppublish
SO  - Structure. 1999 Nov 15;7(11):1427-37. doi: 10.1016/s0969-2126(00)80032-5.