1hkb: Difference between revisions
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|PDB= 1hkb |SIZE=350|CAPTION= <scene name='initialview01'>1hkb</scene>, resolution 2.80Å | |PDB= 1hkb |SIZE=350|CAPTION= <scene name='initialview01'>1hkb</scene>, resolution 2.80Å | ||
|SITE= <scene name='pdbsite=6CA:Glc-6-Phosphate+Binding+Site+In+C-Terminal+Domain'>6CA</scene>, <scene name='pdbsite=6CB:Glc-6-Phosphate+Binding+Site+In+C-Terminal+Domain'>6CB</scene>, <scene name='pdbsite=6NA:Glc-6-Phosphate+Binding+Site+In+N-Terminal+Domain'>6NA</scene>, <scene name='pdbsite=6NB:Glc-6-Phosphate+Binding+Site+In+N-Terminal+Domain'>6NB</scene>, <scene name='pdbsite=GCA:Glc+Binding+Site+In+C-Terminal+Domain'>GCA</scene>, <scene name='pdbsite=GCB:Glc+Binding+Site+In+C-Terminal+Domain'>GCB</scene>, <scene name='pdbsite=GNA:Glc+Binding+Site+In+N-Terminal+Domain'>GNA</scene>, <scene name='pdbsite=GNB:Glc+Binding+Site+In+N-Terminal+Domain'>GNB</scene>, <scene name='pdbsite=MCA:Metal+Ion+Binding+Site+In+C-Terminal+Domain'>MCA</scene>, <scene name='pdbsite=MCB:Metal+Ion+Binding+Site+In+C-Terminal+Domain'>MCB</scene>, <scene name='pdbsite=MNA:Metal+Ion+Binding+Site+In+N-Terminal+Domain'>MNA</scene> and <scene name='pdbsite=MNB:Metal+Ion+Binding+Site+In+N-Terminal+Domain'>MNB</scene> | |SITE= <scene name='pdbsite=6CA:Glc-6-Phosphate+Binding+Site+In+C-Terminal+Domain'>6CA</scene>, <scene name='pdbsite=6CB:Glc-6-Phosphate+Binding+Site+In+C-Terminal+Domain'>6CB</scene>, <scene name='pdbsite=6NA:Glc-6-Phosphate+Binding+Site+In+N-Terminal+Domain'>6NA</scene>, <scene name='pdbsite=6NB:Glc-6-Phosphate+Binding+Site+In+N-Terminal+Domain'>6NB</scene>, <scene name='pdbsite=GCA:Glc+Binding+Site+In+C-Terminal+Domain'>GCA</scene>, <scene name='pdbsite=GCB:Glc+Binding+Site+In+C-Terminal+Domain'>GCB</scene>, <scene name='pdbsite=GNA:Glc+Binding+Site+In+N-Terminal+Domain'>GNA</scene>, <scene name='pdbsite=GNB:Glc+Binding+Site+In+N-Terminal+Domain'>GNB</scene>, <scene name='pdbsite=MCA:Metal+Ion+Binding+Site+In+C-Terminal+Domain'>MCA</scene>, <scene name='pdbsite=MCB:Metal+Ion+Binding+Site+In+C-Terminal+Domain'>MCB</scene>, <scene name='pdbsite=MNA:Metal+Ion+Binding+Site+In+N-Terminal+Domain'>MNA</scene> and <scene name='pdbsite=MNB:Metal+Ion+Binding+Site+In+N-Terminal+Domain'>MNB</scene> | ||
|LIGAND= <scene name='pdbligand= | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=G6P:ALPHA-D-GLUCOSE-6-PHOSPHATE'>G6P</scene>, <scene name='pdbligand=GLC:GLUCOSE'>GLC</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/Hexokinase Hexokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.1 2.7.1.1] | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Hexokinase Hexokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.1 2.7.1.1] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1hkb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hkb OCA], [http://www.ebi.ac.uk/pdbsum/1hkb PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1hkb RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
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. | 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. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Honzatko, R B.]] | [[Category: Honzatko, R B.]] | ||
[[Category: Zeng, C.]] | [[Category: Zeng, C.]] | ||
[[Category: allosteric enzyme]] | [[Category: allosteric enzyme]] | ||
[[Category: glucose]] | [[Category: glucose]] | ||
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[[Category: phosphotransferase]] | [[Category: phosphotransferase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:06:52 2008'' | ||
Revision as of 21:06, 30 March 2008
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| , resolution 2.80Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | , , , , , , , , , , and | ||||||
| Ligands: | , , | ||||||
| Activity: | Hexokinase, with EC number 2.7.1.1 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF RECOMBINANT HUMAN BRAIN HEXOKINASE TYPE I COMPLEXED WITH GLUCOSE AND GLUCOSE-6-PHOSPHATE
OverviewOverview
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.
About this StructureAbout this Structure
1HKB is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
The mechanism of regulation of hexokinase: new insights from the crystal structure of recombinant human brain hexokinase complexed with glucose and glucose-6-phosphate., Aleshin AE, Zeng C, Bourenkov GP, Bartunik HD, Fromm HJ, Honzatko RB, Structure. 1998 Jan 15;6(1):39-50. PMID:9493266
Page seeded by OCA on Sun Mar 30 21:06:52 2008