1hkb: Difference between revisions
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[[Image:1hkb.gif|left|200px]]<br /> | [[Image:1hkb.gif|left|200px]]<br /><applet load="1hkb" size="450" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1hkb" size="450" color="white" frame="true" align="right" spinBox="true" | |||
caption="1hkb, resolution 2.80Å" /> | caption="1hkb, resolution 2.80Å" /> | ||
'''CRYSTAL STRUCTURE OF RECOMBINANT HUMAN BRAIN HEXOKINASE TYPE I COMPLEXED WITH GLUCOSE AND GLUCOSE-6-PHOSPHATE'''<br /> | '''CRYSTAL STRUCTURE OF RECOMBINANT HUMAN BRAIN HEXOKINASE TYPE I COMPLEXED WITH GLUCOSE AND GLUCOSE-6-PHOSPHATE'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
1HKB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with GLC, G6P and CA as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] | 1HKB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with GLC, G6P and CA as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Known structural/functional Sites: <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>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1HKB OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: phosphotransferase]] | [[Category: phosphotransferase]] | ||
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Revision as of 17:19, 18 December 2007
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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.
DiseaseDisease
Known disease associated with this structure: Hemolytic anemia due to hexokinase deficiency OMIM:[142600]
About this StructureAbout this Structure
1HKB is a Single protein structure of sequence from Homo sapiens with GLC, G6P and CA as ligands. Active as Hexokinase, with EC number 2.7.1.1 Known structural/functional Sites: , , , , , , , , , , and . 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
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