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| [[Image:1hkb.gif|left|200px]]<br /><applet load="1hkb" size="450" color="white" frame="true" align="right" spinBox="true"
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| caption="1hkb, resolution 2.80Å" />
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| '''CRYSTAL STRUCTURE OF RECOMBINANT HUMAN BRAIN HEXOKINASE TYPE I COMPLEXED WITH GLUCOSE AND GLUCOSE-6-PHOSPHATE'''<br />
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| ==Overview== | | ==CRYSTAL STRUCTURE OF RECOMBINANT HUMAN BRAIN HEXOKINASE TYPE I COMPLEXED WITH GLUCOSE AND GLUCOSE-6-PHOSPHATE== |
| 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.
| | <StructureSection load='1hkb' size='340' side='right'caption='[[1hkb]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == |
| | <table><tr><td colspan='2'>[[1hkb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HKB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HKB FirstGlance]. <br> |
| | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</td></tr> |
| | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=G6P:ALPHA-D-GLUCOSE-6-PHOSPHATE'>G6P</scene></td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1hkb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hkb OCA], [https://pdbe.org/1hkb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hkb RCSB], [https://www.ebi.ac.uk/pdbsum/1hkb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hkb ProSAT]</span></td></tr> |
| | </table> |
| | == Disease == |
| | [https://www.uniprot.org/uniprot/HXK1_HUMAN HXK1_HUMAN] Defects in HK1 are the cause of hexokinase deficiency (HK deficiency) [MIM:[https://omim.org/entry/235700 235700]. HK deficiency is a rare autosomal recessive disease with nonspherocytic hemolytic anemia as the predominant clinical feature. |
| | == Function == |
| | [https://www.uniprot.org/uniprot/HXK1_HUMAN HXK1_HUMAN] |
| | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> |
| | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hk/1hkb_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> |
| | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1hkb ConSurf]. |
| | <div style="clear:both"></div> |
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| ==Disease== | | ==See Also== |
| 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]]
| | *[[Hexokinase 3D structures|Hexokinase 3D structures]] |
| | | __TOC__ |
| ==About this Structure==
| | </StructureSection> |
| 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].
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| ==Reference==
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| 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9493266 9493266]
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| [[Category: Hexokinase]]
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| [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| [[Category: Single protein]] | | [[Category: Large Structures]] |
| [[Category: Aleshin, A.E.]] | | [[Category: Aleshin AE]] |
| [[Category: Bartunik, H.D.]] | | [[Category: Bartunik HD]] |
| [[Category: Burenkov, G.P.]] | | [[Category: Burenkov GP]] |
| [[Category: Fromm, H.J.]] | | [[Category: Fromm HJ]] |
| [[Category: Honzatko, R.B.]] | | [[Category: Honzatko RB]] |
| [[Category: Zeng, C.]] | | [[Category: Zeng C]] |
| [[Category: CA]]
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| [[Category: G6P]]
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| [[Category: GLC]]
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| [[Category: allosteric enzyme]]
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| [[Category: glucose]]
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| [[Category: glucose-6-phosphate]]
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| [[Category: glycolysis]]
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| [[Category: phosphotransferase]]
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| ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 16:29:07 2007''
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