3vf6 - Revision history

OCA at 10:35, 1 March 2024

2024-03-01T10:35:38Z

←Older revision		Revision as of 10:35, 1 March 2024
Line 3:		Line 3:
	<StructureSection load='3vf6' size='340' side='right'caption='[[3vf6]], [[Resolution\|resolution]] 1.86Å' scene=''>		<StructureSection load='3vf6' size='340' side='right'caption='[[3vf6]], [[Resolution\|resolution]] 1.86Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3vf6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VF6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VF6 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3vf6]] 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=3VF6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VF6 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0H6:6-({(2S)-3-CYCLOPENTYL-2-[4-(TRIFLUOROMETHYL)-1H-IMIDAZOL-1-YL]PROPANOYL}AMINO)PYRIDINE-3-CARBOXYLIC+ACID'>0H6</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene~~></td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.86Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3s41\|3s41]], [[3vev\|3vev]]</div></td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0H6:6-({(2S)-3-CYCLOPENTYL-2-[4-(TRIFLUOROMETHYL)-1H-IMIDAZOL-1-YL]PROPANOYL}AMINO)PYRIDINE-3-CARBOXYLIC+ACID'>0H6</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GCK ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>~~	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></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=3vf6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vf6 OCA], [https://pdbe.org/3vf6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vf6 RCSB], [https://www.ebi.ac.uk/pdbsum/3vf6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vf6 ProSAT]</span></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=3vf6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vf6 OCA], [https://pdbe.org/3vf6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vf6 RCSB], [https://www.ebi.ac.uk/pdbsum/3vf6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vf6 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== 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>	+	[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 ==		== 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.	+	[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.
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Human glucokinase (GK) is a principal regulating sensor of plasma glucose levels. Mutations that inactivate GK are linked to diabetes, and ones that activate it are associated with hypoglycemia. Unique kinetic properties equip GK for its regulatory role: although it has weak basal affinity for glucose, positive cooperativity in its binding of glucose causes a rapid increase in catalytic activity when plasma glucose concentrations rise above euglycemic levels. In clinical trials, small molecule GK activators (GKA) have been efficacious in lowering plasma glucose and enhancing glucose-stimulated insulin secretion (GSIS), but they carry a risk of overly activating GK and causing hypoglycemia. The theoretical models proposed to date attribute the positive cooperativity of GK to the existence of distinct protein conformations that interconvert slowly and exhibit different affinities for glucose. Here we report the respective crystal structures of the catalytic complex of GK and of a GK/glucose complex in a wide-open conformation. To assess conformations of GK in solution, we also carried out small angle X-ray scattering (SAXS) experiments. The results showed that glucose dose-dependently converts GK from an apo conformation to an active open conformation. Compared to wild type GK, activating mutants required notably lower concentrations of glucose to be converted to the active open conformation. GKAs decreased the level of glucose required for GK activation, and different compounds demonstrated distinct activation profiles. These results lead us to propose a modified mnemonic model to explain cooperativity in GK. Our findings may offer new approaches for designing GKA with reduced hypoglycemic risk.	+
-		+
-	Insights into the mechanism of glucokinase activation: observation of multiple distinct protein conformations.,Liu S, Ammirati MJ, Song X, Knafels JD, Zhang J, Greasley SE, Pfefferkorn JA, Qiu X J Biol Chem. 2012 Feb 1. PMID:22298776<ref>PMID:22298776</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3vf6" style="background-color:#fffaf0;"></div>~~	+

	==See Also==		==See Also==
Line 30:		Line 19:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Glucokinase]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Human~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Liu, S]]	+	[[Category: Liu S]]
-	~~[[Category: Catalysis reaction]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transferase-transferase activator complex~~]]	+

OCA at 18:42, 27 July 2022

2022-07-27T18:42:17Z

←Older revision		Revision as of 18:42, 27 July 2022
Line 1:		Line 1:

	==Glucokinase in complex with glucose and activator==		==Glucokinase in complex with glucose and activator==
-	<StructureSection load='3vf6' size='340' side='right' caption='[[3vf6]], [[Resolution\|resolution]] 1.86Å' scene=''>	+	<StructureSection load='3vf6' size='340' side='right'caption='[[3vf6]], [[Resolution\|resolution]] 1.86Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3vf6]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VF6 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3VF6 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3vf6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VF6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VF6 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0H6:6-({(2S)-3-CYCLOPENTYL-2-[4-(TRIFLUOROMETHYL)-1H-IMIDAZOL-1-YL]PROPANOYL}AMINO)PYRIDINE-3-CARBOXYLIC+ACID'>0H6</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0H6:6-({(2S)-3-CYCLOPENTYL-2-[4-(TRIFLUOROMETHYL)-1H-IMIDAZOL-1-YL]PROPANOYL}AMINO)PYRIDINE-3-CARBOXYLIC+ACID'>0H6</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3s41\|3s41]], [[3vev\|3vev]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3s41\|3s41]], [[3vev\|3vev]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GCK ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GCK ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3vf6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vf6 OCA], [~~http~~://pdbe.org/3vf6 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3vf6 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3vf6 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3vf6 ProSAT]</span></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=3vf6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vf6 OCA], [https://pdbe.org/3vf6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vf6 RCSB], [https://www.ebi.ac.uk/pdbsum/3vf6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vf6 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://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:[~~http~~://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:[~~http~~://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>	+	[[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 ==		== Function ==
-	[[~~http~~://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.	+	[[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.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 25:

	==See Also==		==See Also==
-	*[[Hexokinase\|Hexokinase]]	+	*[[Hexokinase 3D structures\|Hexokinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 32:		Line 32:
	[[Category: Glucokinase]]		[[Category: Glucokinase]]
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Liu, S]]		[[Category: Liu, S]]
	[[Category: Catalysis reaction]]		[[Category: Catalysis reaction]]
	[[Category: Transferase]]		[[Category: Transferase]]
	[[Category: Transferase-transferase activator complex]]		[[Category: Transferase-transferase activator complex]]

OCA at 14:37, 5 August 2016

2016-08-05T14:37:34Z

←Older revision		Revision as of 14:37, 5 August 2016
Line 1:		Line 1:
-	{{STRUCTURE_3vf6\| PDB=3vf6 \| SCENE= }}
-	===Glucokinase in complex with glucose and activator===
-	{{ABSTRACT_PUBMED_22298776}}

-	==Disease==	+	==Glucokinase in complex with glucose and activator==
-	[[http://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:[http://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:[http://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>	+	<StructureSection load='3vf6' size='340' side='right' caption='[[3vf6]], [[Resolution\|resolution]] 1.86Å' scene=''>
-		+	== Structural highlights ==
-	==Function==	+	<table><tr><td colspan='2'>[[3vf6]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VF6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VF6 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0H6:6-({(2S)-3-CYCLOPENTYL-2-[4-(TRIFLUOROMETHYL)-1H-IMIDAZOL-1-YL]PROPANOYL}AMINO)PYRIDINE-3-CARBOXYLIC+ACID'>0H6</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3s41\|3s41]], [[3vev\|3vev]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GCK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3vf6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vf6 OCA], [http://pdbe.org/3vf6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3vf6 RCSB], [http://www.ebi.ac.uk/pdbsum/3vf6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3vf6 ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://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:[http://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:[http://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 ==
	[[http://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.		[[http://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.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Human glucokinase (GK) is a principal regulating sensor of plasma glucose levels. Mutations that inactivate GK are linked to diabetes, and ones that activate it are associated with hypoglycemia. Unique kinetic properties equip GK for its regulatory role: although it has weak basal affinity for glucose, positive cooperativity in its binding of glucose causes a rapid increase in catalytic activity when plasma glucose concentrations rise above euglycemic levels. In clinical trials, small molecule GK activators (GKA) have been efficacious in lowering plasma glucose and enhancing glucose-stimulated insulin secretion (GSIS), but they carry a risk of overly activating GK and causing hypoglycemia. The theoretical models proposed to date attribute the positive cooperativity of GK to the existence of distinct protein conformations that interconvert slowly and exhibit different affinities for glucose. Here we report the respective crystal structures of the catalytic complex of GK and of a GK/glucose complex in a wide-open conformation. To assess conformations of GK in solution, we also carried out small angle X-ray scattering (SAXS) experiments. The results showed that glucose dose-dependently converts GK from an apo conformation to an active open conformation. Compared to wild type GK, activating mutants required notably lower concentrations of glucose to be converted to the active open conformation. GKAs decreased the level of glucose required for GK activation, and different compounds demonstrated distinct activation profiles. These results lead us to propose a modified mnemonic model to explain cooperativity in GK. Our findings may offer new approaches for designing GKA with reduced hypoglycemic risk.

-	~~==About this Structure==~~	+	Insights into the mechanism of glucokinase activation: observation of multiple distinct protein conformations.,Liu S, Ammirati MJ, Song X, Knafels JD, Zhang J, Greasley SE, Pfefferkorn JA, Qiu X J Biol Chem. 2012 Feb 1. PMID:22298776<ref>PMID:22298776</ref>
-	~~[[3vf6]] is a 1 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=3VF6 OCA].~~	+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 3vf6" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Hexokinase\|Hexokinase]]		*[[Hexokinase\|Hexokinase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:022298776</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Glucokinase]]		[[Category: Glucokinase]]
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
-	[[Category: Liu, S.]]	+	[[Category: Liu, S]]
	[[Category: Catalysis reaction]]		[[Category: Catalysis reaction]]
	[[Category: Transferase]]		[[Category: Transferase]]
	[[Category: Transferase-transferase activator complex]]		[[Category: Transferase-transferase activator complex]]

OCA at 00:05, 25 March 2013

2013-03-25T00:05:09Z

←Older revision		Revision as of 00:05, 25 March 2013
Line 1:		Line 1:
-	[[Image:3vf6.png\|left\|200px]]
-
	{{STRUCTURE_3vf6\| PDB=3vf6 \| SCENE= }}		{{STRUCTURE_3vf6\| PDB=3vf6 \| SCENE= }}
-
	===Glucokinase in complex with glucose and activator===		===Glucokinase in complex with glucose and activator===
		+	{{ABSTRACT_PUBMED_22298776}}

-	~~{{ABSTRACT_PUBMED_22298776}}~~	+	==Disease==
		+	[[http://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:[http://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:[http://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==
		+	[[http://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.

	==About this Structure==		==About this Structure==
Line 14:		Line 16:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:022298776</ref><references group="xtra"/>	+	<ref group="xtra">PMID:022298776</ref><references group="xtra"/><references/>
	[[Category: Glucokinase]]		[[Category: Glucokinase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]

OCA at 12:03, 20 October 2012

2012-10-20T12:03:40Z

←Older revision		Revision as of 12:03, 20 October 2012
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	[[Image:3vf6.png\|left\|200px]]		[[Image:3vf6.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_3vf6", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_3vf6\| PDB=3vf6 \| SCENE= }}		{{STRUCTURE_3vf6\| PDB=3vf6 \| SCENE= }}

	===Glucokinase in complex with glucose and activator===		===Glucokinase in complex with glucose and activator===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_22298776}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 22298776 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_22298776}}		{{ABSTRACT_PUBMED_22298776}}

	==About this Structure==		==About this Structure==
	[[3vf6]] is a 1 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=3VF6 OCA].		[[3vf6]] is a 1 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=3VF6 OCA].
		+
		+	==See Also==
		+	*[[Hexokinase\|Hexokinase]]

	==Reference==		==Reference==

OCA at 05:57, 11 April 2012

2012-04-11T05:57:23Z

←Older revision		Revision as of 05:57, 11 April 2012
Line 11:		Line 11:
	===Glucokinase in complex with glucose and activator===		===Glucokinase in complex with glucose and activator===

		+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_22298776}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 22298776 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_22298776}}

	==About this Structure==		==About this Structure==
	[[3vf6]] is a 1 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=3VF6 OCA].		[[3vf6]] is a 1 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=3VF6 OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:022298776</ref><references group="xtra"/>
	[[Category: Glucokinase]]		[[Category: Glucokinase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]

OCA at 05:44, 15 February 2012

2012-02-15T05:44:50Z

←Older revision		Revision as of 05:44, 15 February 2012
Line 1:		Line 1:
-	[[Image:3vf6.~~jpg~~\|left\|200px]]	+	[[Image:3vf6.png\|left\|200px]]

	<!--		<!--

OCA at 06:43, 8 February 2012

2012-02-08T06:43:37Z

←Older revision		Revision as of 06:43, 8 February 2012
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-	~~'''Unreleased structure'''~~	+	[[Image:3vf6.jpg\|left\|200px]]

-	The ~~entry 3vf6~~ is ~~ON HOLD~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3vf6", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3vf6\| PDB=3vf6 \| SCENE= }}

-	~~Authors: Liu, S.~~	+	===Glucokinase in complex with glucose and activator===

-	~~Description~~: Glucokinase ~~in complex with glucose and~~ activator	+
		+	==About this Structure==
		+	[[3vf6]] is a 1 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=3VF6 OCA].
		+	[[Category: Glucokinase]]
		+	[[Category: Homo sapiens]]
		+	[[Category: Liu, S.]]
		+	[[Category: Catalysis reaction]]
		+	[[Category: Transferase]]
		+	[[Category: Transferase-transferase activator complex]]

OCA at 06:04, 25 January 2012

2012-01-25T06:04:27Z

←Older revision		Revision as of 06:04, 25 January 2012
Line 3:		Line 3:
	The entry 3vf6 is ON HOLD		The entry 3vf6 is ON HOLD

-	Authors: Liu, ~~Shenping~~	+	Authors: Liu, S.

-	Description: ~~glucokinase~~ in complex with glucose and activator	+	Description: Glucokinase in complex with glucose and activator

OCA: Protected "3vf6" [edit=sysop:move=sysop]

2012-01-18T10:21:34Z

Protected "3vf6" [edit=sysop:move=sysop]

←Older revision

Revision as of 10:21, 18 January 2012