1qha
From Proteopedia
(Difference between revisions)
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| - | + | ==HUMAN HEXOKINASE TYPE I COMPLEXED WITH ATP ANALOGUE AMP-PNP== | |
| - | + | <StructureSection load='1qha' size='340' side='right' caption='[[1qha]], [[Resolution|resolution]] 2.25Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[1qha]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QHA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1QHA FirstGlance]. <br> | |
| - | ==Disease== | + | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=G6P:ALPHA-D-GLUCOSE-6-PHOSPHATE'>G6P</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene><br> |
| + | <tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr> | ||
| + | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1qha FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qha OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1qha RCSB], [http://www.ebi.ac.uk/pdbsum/1qha PDBsum]</span></td></tr> | ||
| + | <table> | ||
| + | == Disease == | ||
[[http://www.uniprot.org/uniprot/HXK1_HUMAN HXK1_HUMAN]] Defects in HK1 are the cause of hexokinase deficiency (HK deficiency) [MIM:[http://omim.org/entry/235700 235700]]. HK deficiency is a rare autosomal recessive disease with nonspherocytic hemolytic anemia as the predominant clinical feature. | [[http://www.uniprot.org/uniprot/HXK1_HUMAN HXK1_HUMAN]] Defects in HK1 are the cause of hexokinase deficiency (HK deficiency) [MIM:[http://omim.org/entry/235700 235700]]. HK deficiency is a rare autosomal recessive disease with nonspherocytic hemolytic anemia as the predominant clinical feature. | ||
| + | == Function == | ||
| - | == | + | == 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/qh/1qha_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/chain_selection.php?pdb_ID=2ata ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | BACKGROUND: Hexokinase I sets the pace of glycolysis in the brain, catalyzing the ATP-dependent phosphorylation of glucose. The catalytic properties of hexokinase I are dependent on product inhibition as well as on the action of phosphate. In vivo, a large fraction of hexokinase I is bound to the mitochondrial outer membrane, where the enzyme adopts a tetrameric assembly. The mitochondrion-bound hexokinase I is believed to optimize the ATP/ADP exchange between glucose phosphorylation and the mitochondrial oxidative phosphorylation reactions. RESULTS: The crystal structure of human hexokinase I has been determined at 2.25 A resolution. The overall structure of the enzyme is in keeping with the closed conformation previously observed in yeast hexokinase. One molecule of the ATP analogue AMP-PNP is bound to each N-terminal domain of the dimeric enzyme in a surface cleft, showing specific interactions with the nucleotide, and localized positive electrostatic potential. The molecular symmetry brings the two bound AMP-PNP molecules, at the centre of two extended surface regions, to a common side of the dimeric hexokinase I molecule. CONCLUSIONS: The binding of AMP-PNP to a protein site separated from the catalytic centre of human hexokinase I can be related to the role played by some nucleotides in dissociating the enzyme from the mitochondrial membrane, and helps in defining the molecular regions of hexokinase I that are expected to be in contact with the mitochondrion. The structural information presented here is in keeping with monoclonal antibody mapping of the free and mitochondrion-bound forms of the enzyme, and with sequence analysis of hexokinases that differ in their mitochondria binding properties. | ||
| + | |||
| + | Binding of non-catalytic ATP to human hexokinase I highlights the structural components for enzyme-membrane association control.,Rosano C, Sabini E, Rizzi M, Deriu D, Murshudov G, Bianchi M, Serafini G, Magnani M, Bolognesi M Structure. 1999 Nov 15;7(11):1427-37. PMID:10574795<ref>PMID:10574795</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
==See Also== | ==See Also== | ||
*[[Hexokinase|Hexokinase]] | *[[Hexokinase|Hexokinase]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | + | __TOC__ | |
| + | </StructureSection> | ||
[[Category: Hexokinase]] | [[Category: Hexokinase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
Revision as of 17:34, 29 September 2014
HUMAN HEXOKINASE TYPE I COMPLEXED WITH ATP ANALOGUE AMP-PNP
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