6e0i - Revision history

OCA at 14:38, 13 March 2024

OCA — Wed, 13 Mar 2024 14:38:15 GMT

←Older revision		Revision as of 14:38, 13 March 2024
Line 3:		Line 3:
	<StructureSection load='6e0i' size='340' side='right'caption='[[6e0i]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='6e0i' size='340' side='right'caption='[[6e0i]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6e0i]] 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=6E0I OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6E0I FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6e0i]] 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=6E0I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6E0I FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=HKG:1-{4-[5-({3-[(2-methylpyridin-3-yl)oxy]-5-[(pyridin-2-yl)sulfanyl]pyridin-2-yl}amino)-1,2,4-thiadiazol-3-yl]piperidin-1-yl}ethan-1-one'>HKG</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]] 1.9Å</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=HKG:1-{4-[5-({3-[(2-methylpyridin-3-yl)oxy]-5-[(pyridin-2-yl)sulfanyl]pyridin-2-yl}amino)-1,2,4-thiadiazol-3-yl]piperidin-1+-yl}ethan-1-one'>HKG</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=6e0i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e0i OCA], [https://pdbe.org/6e0i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6e0i RCSB], [https://www.ebi.ac.uk/pdbsum/6e0i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6e0i ProSAT]</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=6e0i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e0i OCA], [~~http~~://pdbe.org/6e0i PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6e0i RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6e0i PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6e0i 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;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Glucose flux through glucokinase (GK) controls insulin release from the pancreas in response to high levels of glucose. Flux through GK is also responsible for reducing hepatic glucose output. Since many individuals with type 2 diabetes appear to have an inadequacy or defect in one or both of these processes, identifying compounds that can activate GK could provide a therapeutic benefit. Herein we report the further structure activity studies of a novel series of glucokinase activators (GKA). These studies led to the identification of pyridine 72 as a potent GKA that lowered post-prandial glucose in normal C57BL/6J mice, and after 14d dosing in ob/ob mice.	+

-	Discovery and preclinical development of AR453588 as an anti-diabetic glucokinase activator.,Hinklin RJ, Baer BR, Boyd SA, Chicarelli MD, Condroski KR, DeWolf WE Jr, Fischer J, Frank M, Hingorani GP, Lee PA, Neitzel NA, Pratt SA, Singh A, Sullivan FX, Turner T, Voegtli WC, Wallace EM, Williams L, Aicher TD Bioorg Med Chem. 2020 Jan 1;28(1):115232. doi: 10.1016/j.bmc.2019.115232. Epub, 2019 Dec 2. PMID:31818630<ref>PMID:31818630</ref>	+	==See Also==
-		+	*[[Hexokinase 3D structures\|Hexokinase 3D structures]]
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class~~=~~"pdbe-citations 6e0i" style~~=~~"background-color:#fffaf0;"></div>~~	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Glucokinase]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Human~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Aicher~~, T D~~]]	+	[[Category: Aicher TD]]
-	[[Category: Baer~~, B R~~]]	+	[[Category: Baer BR]]
-	[[Category: Boyd~~, S A~~]]	+	[[Category: Boyd SA]]
-	[[Category: Chicarelli~~, M D~~]]	+	[[Category: Chicarelli MD]]
-	[[Category: Condroski~~, K R~~]]	+	[[Category: Condroski KR]]
-	[[Category: DeWolf~~, W E~~]]	+	[[Category: DeWolf WE]]
-	[[Category: Fischer, J]]	+	[[Category: Fischer J]]
-	[[Category: Frank, M]]	+	[[Category: Frank M]]
-	[[Category: Hingorani~~, G P~~]]	+	[[Category: Hingorani GP]]
-	[[Category: Hinklin~~, R J~~]]	+	[[Category: Hinklin RJ]]
-	[[Category: Lee~~, P A~~]]	+	[[Category: Lee PA]]
-	[[Category: Neitzel~~, N A~~]]	+	[[Category: Neitzel NA]]
-	[[Category: Pratt~~, S A~~]]	+	[[Category: Pratt SA]]
-	[[Category: Singh, A]]	+	[[Category: Singh A]]
-	[[Category: Sullivan~~, F X~~]]	+	[[Category: Sullivan FX]]
-	[[Category: Turner, T]]	+	[[Category: Turner T]]
-	[[Category: Voegtli~~, W C~~]]	+	[[Category: Voegtli WC]]
-	[[Category: Wallace~~, E M~~]]	+	[[Category: Wallace EM]]
-	[[Category: Williams, L]]	+	[[Category: Williams L]]
-	~~[[Category: Glucokinase activator]]~~	+
-	~~[[Category: Structure-aided design]]~~	+
-	~~[[Category: Structure-based design]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex]]~~	+
-	~~[[Category: Type ii diabetes~~]]	+

OCA at 16:31, 22 January 2020

OCA — Wed, 22 Jan 2020 16:31:45 GMT

←Older revision		Revision as of 16:31, 22 January 2020
Line 3:		Line 3:
	<StructureSection load='6e0i' size='340' side='right'caption='[[6e0i]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='6e0i' size='340' side='right'caption='[[6e0i]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6e0i]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E0I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E0I FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6e0i]] 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=6E0I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E0I FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=HKG:1-{4-[5-({3-[(2-methylpyridin-3-yl)oxy]-5-[(pyridin-2-yl)sulfanyl]pyridin-2-yl}amino)-1,2,4-thiadiazol-3-yl]piperidin-1-yl}ethan-1-one'>HKG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=HKG:1-{4-[5-({3-[(2-methylpyridin-3-yl)oxy]-5-[(pyridin-2-yl)sulfanyl]pyridin-2-yl}amino)-1,2,4-thiadiazol-3-yl]piperidin-1-yl}ethan-1-one'>HKG</scene></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='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=6e0i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e0i OCA], [http://pdbe.org/6e0i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e0i RCSB], [http://www.ebi.ac.uk/pdbsum/6e0i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e0i ProSAT]</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=6e0i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e0i OCA], [http://pdbe.org/6e0i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e0i RCSB], [http://www.ebi.ac.uk/pdbsum/6e0i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e0i ProSAT]</span></td></tr>
Line 12:		Line 13:
	== 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.		[[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 ==
		+	Glucose flux through glucokinase (GK) controls insulin release from the pancreas in response to high levels of glucose. Flux through GK is also responsible for reducing hepatic glucose output. Since many individuals with type 2 diabetes appear to have an inadequacy or defect in one or both of these processes, identifying compounds that can activate GK could provide a therapeutic benefit. Herein we report the further structure activity studies of a novel series of glucokinase activators (GKA). These studies led to the identification of pyridine 72 as a potent GKA that lowered post-prandial glucose in normal C57BL/6J mice, and after 14d dosing in ob/ob mice.
		+
		+	Discovery and preclinical development of AR453588 as an anti-diabetic glucokinase activator.,Hinklin RJ, Baer BR, Boyd SA, Chicarelli MD, Condroski KR, DeWolf WE Jr, Fischer J, Frank M, Hingorani GP, Lee PA, Neitzel NA, Pratt SA, Singh A, Sullivan FX, Turner T, Voegtli WC, Wallace EM, Williams L, Aicher TD Bioorg Med Chem. 2020 Jan 1;28(1):115232. doi: 10.1016/j.bmc.2019.115232. Epub, 2019 Dec 2. PMID:31818630<ref>PMID:31818630</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6e0i" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
Line 17:		Line 27:
	</StructureSection>		</StructureSection>
	[[Category: Glucokinase]]		[[Category: Glucokinase]]
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Aicher, T D]]		[[Category: Aicher, T D]]

OCA at 05:40, 10 July 2019

OCA — Wed, 10 Jul 2019 05:40:45 GMT

←Older revision		Revision as of 05:40, 10 July 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6e0i ~~is ON HOLD until Paper Publication~~	+	==Crystal structure of Glucokinase in complex with compound 72==
-		+	<StructureSection load='6e0i' size='340' side='right'caption='[[6e0i]], [[Resolution\|resolution]] 1.90Å' scene=''>
-	~~Authors~~: ~~Hinklin, R~~.J.~~, Baer, B~~.R.~~, Boyd, S~~.A.~~, Chicarelli, M~~.D., ~~Condroski~~, ~~K.R.~~, ~~DeWolf~~, W.E., ~~Fischer, J~~.~~, Frank, M~~.~~, Hingorani, G~~.P.~~, Lee, P~~.A.~~, Neitzel, N~~.A.~~, Pratt, S~~.A.~~, Singh, A~~., ~~Sullivan, F~~.X., ~~Turner, T~~., ~~Voegtli, W~~.C., ~~Wallace, E~~.M., ~~Williams, L~~., ~~Aicher~~, T.D.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6e0i]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E0I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E0I FirstGlance]. <br>
-	~~Description~~: ~~Crystal structure~~ of Glucokinase in ~~complex with compound 72~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=HKG:1-{4-[5-({3-[(2-methylpyridin-3-yl)oxy]-5-[(pyridin-2-yl)sulfanyl]pyridin-2-yl}amino)-1,2,4-thiadiazol-3-yl]piperidin-1-yl}ethan-1-one'>HKG</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<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>
-	[[Category: ~~Dewolf~~, W.E]]	+	<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=6e0i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e0i OCA], [http://pdbe.org/6e0i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e0i RCSB], [http://www.ebi.ac.uk/pdbsum/6e0i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e0i ProSAT]</span></td></tr>
-	[[Category: ~~Aicher~~, ~~T.D~~]]	+	</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.
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Glucokinase]]
		+	[[Category: Large Structures]]
		+	[[Category: Aicher, T D]]
		+	[[Category: Baer, B R]]
		+	[[Category: Boyd, S A]]
		+	[[Category: Chicarelli, M D]]
		+	[[Category: Condroski, K R]]
		+	[[Category: DeWolf, W E]]
		+	[[Category: Fischer, J]]
		+	[[Category: Frank, M]]
		+	[[Category: Hingorani, G P]]
		+	[[Category: Hinklin, R J]]
		+	[[Category: Lee, P A]]
		+	[[Category: Neitzel, N A]]
		+	[[Category: Pratt, S A]]
		+	[[Category: Singh, A]]
		+	[[Category: Sullivan, F X]]
	[[Category: Turner, T]]		[[Category: Turner, T]]
-	[[Category: ~~Pratt~~, ~~S.A]]~~	+	[[Category: Voegtli, W C]]
-	~~[[Category: Sullivan, F.X]]~~	+	[[Category: Wallace, E M]]
-	~~[[Category: Condroski, K.R]]~~	+
-	~~[[Category: Hinklin, R.J]]~~	+
-	~~[[Category: Singh, A]]~~	+
-	~~[[Category: Frank, M~~]]	+
-	[[Category: Wallace, E.M]]	+
	[[Category: Williams, L]]		[[Category: Williams, L]]
-	[[Category: ~~Lee, P.A~~]]	+	[[Category: Glucokinase activator]]
-	[[Category: ~~Hingorani, G.P~~]]	+	[[Category: Structure-aided design]]
-	[[Category: ~~Neitzel, N.A~~]]	+	[[Category: Structure-based design]]
-	[[Category: ~~Chicarelli, M.D~~]]	+	[[Category: Transferase-transferase inhibitor complex]]
-	[[Category: ~~Boyd, S.A]]~~	+	[[Category: Type ii diabetes]]
-	~~[[Category: Voegtli, W.C]]~~	+
-	~~[[Category: Fischer, J]]~~	+
-	~~[[Category: Baer, B.R~~]]	+

OCA at 19:48, 9 August 2018

OCA — Thu, 09 Aug 2018 19:48:00 GMT

←Older revision		Revision as of 19:48, 9 August 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6e0i is ON HOLD	+	The entry 6e0i is ON HOLD until Paper Publication

	Authors: Hinklin, R.J., Baer, B.R., Boyd, S.A., Chicarelli, M.D., Condroski, K.R., DeWolf, W.E., Fischer, J., Frank, M., Hingorani, G.P., Lee, P.A., Neitzel, N.A., Pratt, S.A., Singh, A., Sullivan, F.X., Turner, T., Voegtli, W.C., Wallace, E.M., Williams, L., Aicher, T.D.		Authors: Hinklin, R.J., Baer, B.R., Boyd, S.A., Chicarelli, M.D., Condroski, K.R., DeWolf, W.E., Fischer, J., Frank, M., Hingorani, G.P., Lee, P.A., Neitzel, N.A., Pratt, S.A., Singh, A., Sullivan, F.X., Turner, T., Voegtli, W.C., Wallace, E.M., Williams, L., Aicher, T.D.

OCA: Protected "6e0i" [edit=sysop:move=sysop]

OCA — Wed, 18 Jul 2018 05:32:26 GMT

Protected "6e0i" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:32, 18 July 2018

OCA: New page: '''Unreleased structure''' The entry 6e0i is ON HOLD Authors: Hinklin, R.J., Baer, B.R., Boyd, S.A., Chicarelli, M.D., Condroski, K.R., DeWolf, W.E., Fischer, J., Frank, M., Hingorani, ...

OCA — Wed, 18 Jul 2018 05:32:25 GMT

New page: '''Unreleased structure''' The entry 6e0i is ON HOLD Authors: Hinklin, R.J., Baer, B.R., Boyd, S.A., Chicarelli, M.D., Condroski, K.R., DeWolf, W.E., Fischer, J., Frank, M., Hingorani, ...

New page

'''Unreleased structure'''

The entry 6e0i is ON HOLD

Authors: Hinklin, R.J., Baer, B.R., Boyd, S.A., Chicarelli, M.D., Condroski, K.R., DeWolf, W.E., Fischer, J., Frank, M., Hingorani, G.P., Lee, P.A., Neitzel, N.A., Pratt, S.A., Singh, A., Sullivan, F.X., Turner, T., Voegtli, W.C., Wallace, E.M., Williams, L., Aicher, T.D.

Description: Crystal structure of Glucokinase in complex with compound 72
[[Category: Unreleased Structures]]
[[Category: Dewolf, W.E]]
[[Category: Aicher, T.D]]
[[Category: Turner, T]]
[[Category: Pratt, S.A]]
[[Category: Sullivan, F.X]]
[[Category: Condroski, K.R]]
[[Category: Hinklin, R.J]]
[[Category: Singh, A]]
[[Category: Frank, M]]
[[Category: Wallace, E.M]]
[[Category: Williams, L]]
[[Category: Lee, P.A]]
[[Category: Hingorani, G.P]]
[[Category: Neitzel, N.A]]
[[Category: Chicarelli, M.D]]
[[Category: Boyd, S.A]]
[[Category: Voegtli, W.C]]
[[Category: Fischer, J]]
[[Category: Baer, B.R]]