View source for 3id8


==Ternary complex of human pancreatic glucokinase crystallized with activator, glucose and AMP-PNP==
<StructureSection load='3id8' size='340' side='right'caption='[[3id8]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3id8]] is a 1 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=3ID8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ID8 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]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MRK:2-AMINO-4-FLUORO-5-[(1-METHYL-1H-IMIDAZOL-2-YL)SULFANYL]-N-(1,3-THIAZOL-2-YL)BENZAMIDE'>MRK</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=3id8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3id8 OCA], [https://pdbe.org/3id8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3id8 RCSB], [https://www.ebi.ac.uk/pdbsum/3id8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3id8 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/HXK4_HUMAN HXK4_HUMAN] Defects in GCK are the cause of maturity-onset diabetes of the young type 2 (MODY2) [MIM:[https://omim.org/entry/125851 125851]; also shortened MODY-2. MODY is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.<ref>PMID:1502186</ref> <ref>PMID:1464666</ref> <ref>PMID:1303265</ref> <ref>PMID:8495817</ref> <ref>PMID:8325892</ref> <ref>PMID:8446612</ref> <ref>PMID:8168652</ref> <ref>PMID:9049484</ref> <ref>PMID:10694920</ref> <ref>PMID:9662401</ref> <ref>PMID:10588527</ref> <ref>PMID:11106831</ref> <ref>PMID:11372010</ref>   Defects in GCK are the cause of familial hyperinsulinemic hypoglycemia type 3 (HHF3) [MIM:[https://omim.org/entry/602485 602485]; also known as persistent hyperinsulinemic hypoglycemia of infancy (PHHI) or congenital hyperinsulinism. HHF is the most common cause of persistent hypoglycemia in infancy. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur.<ref>PMID:9435328</ref> 
== Function ==
[https://www.uniprot.org/uniprot/HXK4_HUMAN HXK4_HUMAN] Catalyzes the initial step in utilization of glucose by the beta-cell and liver at physiological glucose concentration. Glucokinase has a high Km for glucose, and so it is effective only when glucose is abundant. The role of GCK is to provide G6P for the synthesis of glycogen. Pancreatic glucokinase plays an important role in modulating insulin secretion. Hepatic glucokinase helps to facilitate the uptake and conversion of glucose by acting as an insulin-sensitive determinant of hepatic glucose usage.
== 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/id/3id8_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=3id8 ConSurf].
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== Publication Abstract from PubMed ==
Glucokinase (GK) catalyses the formation of glucose 6-phosphate from glucose and ATP. A specific feature of GK amongst hexokinases is that it can cycle between active and inactive conformations as a function of glucose concentration, resulting in a unique positive kinetic cooperativity with glucose, which turns GK into a unique key sensor of glucose metabolism, notably in the pancreas. GK is a target of antidiabetic drugs aimed at the activation of GK activity, leading to insulin secretion. Here, the first structures of a GK-glucose complex without activator, of GK-glucose-AMP-PNP and of GK-glucose-AMP-PNP with a bound activator are reported. All these structures are extremely similar, thus demonstrating that binding of GK activators does not result in conformational changes of the active protein but in stabilization of the active form of GK.

The active conformation of human glucokinase is not altered by allosteric activators.,Petit P, Antoine M, Ferry G, Boutin JA, Lagarde A, Gluais L, Vincentelli R, Vuillard L Acta Crystallogr D Biol Crystallogr. 2011 Nov;67(Pt 11):929-35. Epub 2011 Oct 19. PMID:22101819<ref>PMID:22101819</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3id8" style="background-color:#fffaf0;"></div>

==See Also==
*[[Hexokinase 3D structures|Hexokinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Boutin JA]]
[[Category: Ferry G]]
[[Category: Gluais L]]
[[Category: Lagarde A]]
[[Category: Petit P]]
[[Category: Vuillard L]]