1hkc
From Proteopedia
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|PDB= 1hkc |SIZE=350|CAPTION= <scene name='initialview01'>1hkc</scene>, resolution 2.80Å | |PDB= 1hkc |SIZE=350|CAPTION= <scene name='initialview01'>1hkc</scene>, resolution 2.80Å | ||
|SITE= <scene name='pdbsite=GLN:Glc+Binding+Site+In+N-Terminal+Domain'>GLN</scene>, <scene name='pdbsite=MEC:Metal+Ion+Binding+Site+In+C-Terminal+Domain'>MEC</scene>, <scene name='pdbsite=MEN:Metal+Ion+Binding+Site+In+N-Terminal+Domain'>MEN</scene>, <scene name='pdbsite=PIC:Phosphate+Binding+Site+In+C-Terminal+Domain'>PIC</scene> and <scene name='pdbsite=PIN:Phosphate+Binding+Site+In+N-Terminal+Domain'>PIN</scene> | |SITE= <scene name='pdbsite=GLN:Glc+Binding+Site+In+N-Terminal+Domain'>GLN</scene>, <scene name='pdbsite=MEC:Metal+Ion+Binding+Site+In+C-Terminal+Domain'>MEC</scene>, <scene name='pdbsite=MEN:Metal+Ion+Binding+Site+In+N-Terminal+Domain'>MEN</scene>, <scene name='pdbsite=PIC:Phosphate+Binding+Site+In+C-Terminal+Domain'>PIC</scene> and <scene name='pdbsite=PIN:Phosphate+Binding+Site+In+N-Terminal+Domain'>PIN</scene> | ||
| - | |LIGAND= <scene name='pdbligand=GLC:GLUCOSE'>GLC</scene>, <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=GLC:GLUCOSE'>GLC</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=1hkc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hkc OCA], [http://www.ebi.ac.uk/pdbsum/1hkc PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1hkc RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
Hexokinase I, the pacemaker of glycolysis in brain tissue and red blood cells, is comprised of two similar domains fused into a single polypeptide chain. The C-terminal half of hexokinase I is catalytically active, whereas the N-terminal half is necessary for the relief of product inhibition by phosphate. A crystalline complex of recombinant human hexokinase I with glucose and phosphate (2.8 A resolution) reveals a single binding site for phosphate and glucose at the N-terminal half of the enzyme. Glucose and phosphate stabilize the N-terminal half in a closed conformation. Unexpectedly, glucose binds weakly to the C-terminal half of the enzyme and does not by itself stabilize a closed conformation. Evidently a stable, closed C-terminal half requires either ATP or glucose 6-phosphate along with glucose. The crystal structure here, in conjunction with other studies in crystallography and directed mutation, puts the phosphate regulatory site at the N-terminal half, the site of potent product inhibition at the C-terminal half, and a secondary site for the weak interaction of glucose 6-phosphate at the N-terminal half of the enzyme. The relevance of crystal structures of hexokinase I to the properties of monomeric hexokinase I and oligomers of hexokinase I bound to the surface of mitochondria is discussed. | Hexokinase I, the pacemaker of glycolysis in brain tissue and red blood cells, is comprised of two similar domains fused into a single polypeptide chain. The C-terminal half of hexokinase I is catalytically active, whereas the N-terminal half is necessary for the relief of product inhibition by phosphate. A crystalline complex of recombinant human hexokinase I with glucose and phosphate (2.8 A resolution) reveals a single binding site for phosphate and glucose at the N-terminal half of the enzyme. Glucose and phosphate stabilize the N-terminal half in a closed conformation. Unexpectedly, glucose binds weakly to the C-terminal half of the enzyme and does not by itself stabilize a closed conformation. Evidently a stable, closed C-terminal half requires either ATP or glucose 6-phosphate along with glucose. The crystal structure here, in conjunction with other studies in crystallography and directed mutation, puts the phosphate regulatory site at the N-terminal half, the site of potent product inhibition at the C-terminal half, and a secondary site for the weak interaction of glucose 6-phosphate at the N-terminal half of the enzyme. The relevance of crystal structures of hexokinase I to the properties of monomeric hexokinase I and oligomers of hexokinase I bound to the surface of mitochondria is discussed. | ||
| - | |||
| - | ==Disease== | ||
| - | Known disease associated with this structure: Hemolytic anemia due to hexokinase deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142600 142600]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Aleshin, A E.]] | [[Category: Aleshin, A E.]] | ||
[[Category: Honzatko, R B.]] | [[Category: Honzatko, R B.]] | ||
| - | [[Category: GLC]] | ||
| - | [[Category: K]] | ||
| - | [[Category: PO4]] | ||
[[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 21:06:35 2008'' |
Revision as of 18:06, 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 | ||||||
RECOMBINANT HUMAN HEXOKINASE TYPE I COMPLEXED WITH GLUCOSE AND PHOSPHATE
Overview
Hexokinase I, the pacemaker of glycolysis in brain tissue and red blood cells, is comprised of two similar domains fused into a single polypeptide chain. The C-terminal half of hexokinase I is catalytically active, whereas the N-terminal half is necessary for the relief of product inhibition by phosphate. A crystalline complex of recombinant human hexokinase I with glucose and phosphate (2.8 A resolution) reveals a single binding site for phosphate and glucose at the N-terminal half of the enzyme. Glucose and phosphate stabilize the N-terminal half in a closed conformation. Unexpectedly, glucose binds weakly to the C-terminal half of the enzyme and does not by itself stabilize a closed conformation. Evidently a stable, closed C-terminal half requires either ATP or glucose 6-phosphate along with glucose. The crystal structure here, in conjunction with other studies in crystallography and directed mutation, puts the phosphate regulatory site at the N-terminal half, the site of potent product inhibition at the C-terminal half, and a secondary site for the weak interaction of glucose 6-phosphate at the N-terminal half of the enzyme. The relevance of crystal structures of hexokinase I to the properties of monomeric hexokinase I and oligomers of hexokinase I bound to the surface of mitochondria is discussed.
About this Structure
1HKC is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Regulation of hexokinase I: crystal structure of recombinant human brain hexokinase complexed with glucose and phosphate., Aleshin AE, Zeng C, Bartunik HD, Fromm HJ, Honzatko RB, J Mol Biol. 1998 Sep 18;282(2):345-57. PMID:9735292
Page seeded by OCA on Sun Mar 30 21:06:35 2008
