1hkb
From Proteopedia
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<StructureSection load='1hkb' size='340' side='right'caption='[[1hkb]], [[Resolution|resolution]] 2.80Å' scene=''> | <StructureSection load='1hkb' size='340' side='right'caption='[[1hkb]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
- | <table><tr><td colspan='2'>[[1hkb]] is a 2 chain structure with sequence from [ | + | <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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='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'>[ | + | <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> | </table> | ||
== Disease == | == 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 == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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</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]. | </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> | <div style="clear:both"></div> | ||
- | <div style="background-color:#fffaf0;"> | ||
- | == Publication Abstract from PubMed == | ||
- | 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. | ||
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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:9493266<ref>PMID:9493266</ref> | ||
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- | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
- | </div> | ||
- | <div class="pdbe-citations 1hkb" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Hexokinase 3D structures|Hexokinase 3D structures]] | *[[Hexokinase 3D structures|Hexokinase 3D structures]] | ||
- | == References == | ||
- | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
- | [[Category: | + | [[Category: Homo sapiens]] |
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[[Category: Large Structures]] | [[Category: Large Structures]] | ||
- | [[Category: Aleshin | + | [[Category: Aleshin AE]] |
- | [[Category: Bartunik | + | [[Category: Bartunik HD]] |
- | [[Category: Burenkov | + | [[Category: Burenkov GP]] |
- | [[Category: Fromm | + | [[Category: Fromm HJ]] |
- | [[Category: Honzatko | + | [[Category: Honzatko RB]] |
- | [[Category: Zeng | + | [[Category: Zeng C]] |
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Current revision
CRYSTAL STRUCTURE OF RECOMBINANT HUMAN BRAIN HEXOKINASE TYPE I COMPLEXED WITH GLUCOSE AND GLUCOSE-6-PHOSPHATE
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