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[[Image:1dgk.jpg|left|200px]]<br /><applet load="1dgk" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1dgk, resolution 2.8&Aring;" />
'''MUTANT MONOMER OF RECOMBINANT HUMAN HEXOKINASE TYPE I WITH GLUCOSE AND ADP IN THE ACTIVE SITE'''<br />


==Overview==
==MUTANT MONOMER OF RECOMBINANT HUMAN HEXOKINASE TYPE I WITH GLUCOSE AND ADP IN THE ACTIVE SITE==
Hexokinase I, the pacemaker of glycolysis in brain tissue, is composed of, two structurally similar halves connected by an alpha-helix. The enzyme, dimerizes at elevated protein concentrations in solution and in crystal, structures; however, almost all published data reflect the properties of a, hexokinase I monomer in solution. Crystal structures of mutant forms of, recombinant human hexokinase I, presented here, reveal the enzyme monomer, for the first time. The mutant hexokinases bind both glucose 6-phosphate, and glucose with high affinity to their N and C-terminal halves, and ADP, also with high affinity, to a site near the N terminus of the polypeptide, chain. Exposure of the monomer crystals to ADP in the complete absence of, glucose 6-phosphate reveals a second binding site for adenine nucleotides, at the putative active site (C-half), with conformational changes, extending 15 A to the contact interface between the N and C-halves. The, structures reveal distinct conformational states for the C-half and a, rigid-body rotation of the N-half, as possible elements of a, structure-based mechanism for allosteric regulation of catalysis.
<StructureSection load='1dgk' size='340' side='right'caption='[[1dgk]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1dgk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The February 2004 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''The Glycolytic Enzymes''  by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2004_2 10.2210/rcsb_pdb/mom_2004_2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DGK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1DGK 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]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=1dgk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dgk OCA], [https://pdbe.org/1dgk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1dgk RCSB], [https://www.ebi.ac.uk/pdbsum/1dgk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1dgk 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/dg/1dgk_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=1dgk ConSurf].
<div style="clear:both"></div>


==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>
1DGK 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 <scene name='pdbligand=GLC:'>GLC</scene>, <scene name='pdbligand=PO4:'>PO4</scene> and <scene name='pdbligand=ADP:'>ADP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. The following page contains interesting information on the relation of 1DGK with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb50_1.html The Glycolytic Enzymes]]. 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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DGK OCA].
 
==Reference==
Crystal structures of mutant monomeric hexokinase I reveal multiple ADP binding sites and conformational changes relevant to allosteric regulation., Aleshin AE, Kirby C, Liu X, Bourenkov GP, Bartunik HD, Fromm HJ, Honzatko RB, J Mol Biol. 2000 Mar 3;296(4):1001-15. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10686099 10686099]
[[Category: Hexokinase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: The Glycolytic Enzymes]]
[[Category: The Glycolytic Enzymes]]
[[Category: Aleshin, A.E.]]
[[Category: Aleshin AE]]
[[Category: Bartunik, H.D.]]
[[Category: Bartunik HD]]
[[Category: Bourenkov, G.P.]]
[[Category: Bourenkov GP]]
[[Category: Fromm, H.J.]]
[[Category: Fromm HJ]]
[[Category: Honzatko, R.B.]]
[[Category: Honzatko RB]]
[[Category: Kirby, C.]]
[[Category: Kirby C]]
[[Category: Liu, X.]]
[[Category: Liu X]]
[[Category: ADP]]
[[Category: GLC]]
[[Category: PO4]]
[[Category: brain hexokinase]]
[[Category: mammalian hexokinase 1]]
[[Category: sugar kinase]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 15:39:43 2008''

Latest revision as of 06:53, 7 February 2024

MUTANT MONOMER OF RECOMBINANT HUMAN HEXOKINASE TYPE I WITH GLUCOSE AND ADP IN THE ACTIVE SITE

1dgk, resolution 2.80Å

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