3fr0: Difference between revisions
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< | ==Human glucokinase in complex with 2-amino benzamide activator== | ||
<StructureSection load='3fr0' size='340' side='right'caption='[[3fr0]], [[Resolution|resolution]] 2.70Å' scene=''> | |||
== Structural highlights == | |||
or the | <table><tr><td colspan='2'>[[3fr0]] 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=3FR0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FR0 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]] 2.7Å</td></tr> | |||
- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AJB:2-AMINO-N-(4-METHYL-1,3-THIAZOL-2-YL)-5-[(4-METHYL-4H-1,2,4-TRIAZOL-3-YL)SULFANYL]BENZAMIDE'>AJB</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=3fr0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fr0 OCA], [https://pdbe.org/3fr0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fr0 RCSB], [https://www.ebi.ac.uk/pdbsum/3fr0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fr0 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/fr/3fr0_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=3fr0 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The identification and structure-activity-relationships (SARs) of novel 2-amino benzamide glucokinase activators are described. Compounds in this series were developed to be potent GK activators, and their binding mode to the GK protein was determined by crystal structure analysis. In vivo pharmacokinetic and acute in vivo efficacy studies of compound 18 are also described. | |||
Identification of novel and potent 2-amino benzamide derivatives as allosteric glucokinase activators.,Nishimura T, Iino T, Mitsuya M, Bamba M, Watanabe H, Tsukahara D, Kamata K, Sasaki K, Ohyama S, Hosaka H, Futamura M, Nagata Y, Eiki J Bioorg Med Chem Lett. 2009 Mar 1;19(5):1357-60. Epub 2009 Jan 21. PMID:19188063<ref>PMID:19188063</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3fr0" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Hexokinase 3D structures|Hexokinase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
[[ | |||
== | |||
< | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Kamata K]] | ||