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[[Image:1hkb.gif|left|200px]]<br />
<applet load="1hkb" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1hkb, resolution 2.80&Aring;" />
'''CRYSTAL STRUCTURE OF RECOMBINANT HUMAN BRAIN HEXOKINASE TYPE I COMPLEXED WITH GLUCOSE AND GLUCOSE-6-PHOSPHATE'''<br />


==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]] 2.80&Aring;' 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]] 2.8&#8491;</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>


==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] Structure known Active Sites: 6CA, 6CB, 6NA, 6NB, GCA, GCB, GNA, GNB, MCA, MCB, MNA and MNB. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1HKB OCA].
 
==Reference==
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]
[[Category: Hexokinase]]
[[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]]
[[Category: G6P]]
[[Category: GLC]]
[[Category: allosteric enzyme]]
[[Category: glucose]]
[[Category: glucose-6-phosphate]]
[[Category: glycolysis]]
[[Category: phosphotransferase]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:19:16 2007''

Latest revision as of 10:28, 7 February 2024

CRYSTAL STRUCTURE OF RECOMBINANT HUMAN BRAIN HEXOKINASE TYPE I COMPLEXED WITH GLUCOSE AND GLUCOSE-6-PHOSPHATECRYSTAL STRUCTURE OF RECOMBINANT HUMAN BRAIN HEXOKINASE TYPE I COMPLEXED WITH GLUCOSE AND GLUCOSE-6-PHOSPHATE

Structural highlights

1hkb is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.8Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

HXK1_HUMAN Defects in HK1 are the cause of hexokinase deficiency (HK deficiency) [MIM:235700. HK deficiency is a rare autosomal recessive disease with nonspherocytic hemolytic anemia as the predominant clinical feature.

Function

HXK1_HUMAN

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

1hkb, resolution 2.80Å

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