1jca - Revision history

OCA at 06:48, 30 October 2024

2024-10-30T06:48:57Z

← Older revision		Revision as of 06:48, 30 October 2024
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	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jc/1jca_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jc/1jca_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/~~initialview01~~.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>

OCA at 08:38, 16 August 2023

2023-08-16T08:38:49Z

← Older revision		Revision as of 08:38, 16 August 2023
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	<StructureSection load='1jca' size='340' side='right'caption='[[1jca]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='1jca' size='340' side='right'caption='[[1jca]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1jca]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JCA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JCA FirstGlance]. <br>		<table><tr><td colspan='2'>[[1jca]] is a 4 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=1JCA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JCA FirstGlance]. <br>
	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.5Å</td></tr>
	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"><~~div style~~='~~overflow~~: ~~auto; max-height: 3em;~~'>~~[[1j73\|1j73]]~~</~~div~~></td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=1jca FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jca OCA], [https://pdbe.org/1jca PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1jca RCSB], [https://www.ebi.ac.uk/pdbsum/1jca PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1jca 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=1jca FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jca OCA], [https://pdbe.org/1jca PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1jca RCSB], [https://www.ebi.ac.uk/pdbsum/1jca PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1jca ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[https://www.uniprot.org/uniprot/INS_HUMAN INS_HUMAN]] Defects in INS are the cause of familial hyperproinsulinemia (FHPRI) [MIM:[https://omim.org/entry/176730 176730]].<ref>PMID:3470784</ref> <ref>PMID:2196279</ref> <ref>PMID:4019786</ref> <ref>PMID:1601997</ref> Defects in INS are a cause of diabetes mellitus insulin-dependent type 2 (IDDM2) [MIM:[https://omim.org/entry/125852 125852]]. IDDM2 is a multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.<ref>PMID:18192540</ref> Defects in INS are a cause of diabetes mellitus permanent neonatal (PNDM) [MIM:[https://omim.org/entry/606176 606176]]. PNDM is a rare form of diabetes distinct from childhood-onset autoimmune diabetes mellitus type 1. It is characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Permanent neonatal diabetes requires lifelong therapy.<ref>PMID:17855560</ref> <ref>PMID:18162506</ref> Defects in INS are a cause of maturity-onset diabetes of the young type 10 (MODY10) [MIM:[https://omim.org/entry/613370 613370]]. MODY10 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:18192540</ref> <ref>PMID:18162506</ref> <ref>PMID:20226046</ref>		[https://www.uniprot.org/uniprot/INS_HUMAN INS_HUMAN] Defects in INS are the cause of familial hyperproinsulinemia (FHPRI) [MIM:[https://omim.org/entry/176730 176730].<ref>PMID:3470784</ref> <ref>PMID:2196279</ref> <ref>PMID:4019786</ref> <ref>PMID:1601997</ref> Defects in INS are a cause of diabetes mellitus insulin-dependent type 2 (IDDM2) [MIM:[https://omim.org/entry/125852 125852]. IDDM2 is a multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.<ref>PMID:18192540</ref> Defects in INS are a cause of diabetes mellitus permanent neonatal (PNDM) [MIM:[https://omim.org/entry/606176 606176]. PNDM is a rare form of diabetes distinct from childhood-onset autoimmune diabetes mellitus type 1. It is characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Permanent neonatal diabetes requires lifelong therapy.<ref>PMID:17855560</ref> <ref>PMID:18162506</ref> Defects in INS are a cause of maturity-onset diabetes of the young type 10 (MODY10) [MIM:[https://omim.org/entry/613370 613370]. MODY10 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:18192540</ref> <ref>PMID:18162506</ref> <ref>PMID:20226046</ref>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/INS_HUMAN INS_HUMAN]] Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver.		[https://www.uniprot.org/uniprot/INS_HUMAN INS_HUMAN] Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Burke~~, G T~~]]		[[Category: Burke GT]]
	[[Category: Chu, Y C]]		[[Category: Chu Y-C]]
	[[Category: Hellmich, R]]		[[Category: Hellmich R]]
	[[Category: Jia, W]]		[[Category: Jia W]]
	[[Category: Katsoyannis~~, P G~~]]		[[Category: Katsoyannis PG]]
	[[Category: Nakagawa~~, S H~~]]		[[Category: Nakagawa SH]]
	[[Category: Wan, Z]]		[[Category: Wan Z]]
	[[Category: Weiss~~, M A~~]]		[[Category: Weiss MA]]
	[[Category: Zhao, M]]		[[Category: Zhao M]]
	~~[[Category: A8-lysine human insulin]]~~
	~~[[Category: Hormone-growth factor complex]]~~
	~~[[Category: Insulin receptor~~]]

OCA at 06:38, 11 August 2021

2021-08-11T06:38:47Z

OCA at 09:34, 6 November 2019

2019-11-06T09:34:49Z

← Older revision		Revision as of 09:34, 6 November 2019
Line 1:		Line 1:

	==Non-standard Design of Unstable Insulin Analogues with Enhanced Activity==		==Non-standard Design of Unstable Insulin Analogues with Enhanced Activity==
	<StructureSection load='1jca' size='340' side='right' caption='[[1jca]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='1jca' size='340' side='right'caption='[[1jca]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1jca]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JCA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1JCA FirstGlance]. <br>		<table><tr><td colspan='2'>[[1jca]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JCA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1JCA FirstGlance]. <br>
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	</div>		</div>
	<div class="pdbe-citations 1jca" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1jca" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Insulin 3D Structures\|Insulin 3D Structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Large Structures]]
	[[Category: Burke, G T]]		[[Category: Burke, G T]]
	[[Category: Chu, Y C]]		[[Category: Chu, Y C]]

OCA at 09:09, 17 January 2018

2018-01-17T09:09:31Z

← Older revision		Revision as of 09:09, 17 January 2018
Line 1:		Line 1:

	==Non-standard Design of Unstable Insulin Analogues with Enhanced Activity==		==Non-standard Design of Unstable Insulin Analogues with Enhanced Activity==
	<StructureSection load='1jca' size='340' side='right' caption='[[1jca]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='1jca' size='340' side='right' caption='[[1jca]], [[Resolution\|resolution]] 2.50Å' scene=''>
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	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1j73\|1j73]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1j73\|1j73]]</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=1jca FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jca OCA], [http://pdbe.org/1jca PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1jca RCSB], [http://www.ebi.ac.uk/pdbsum/1jca PDBsum]</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=1jca FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jca OCA], [http://pdbe.org/1jca PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1jca RCSB], [http://www.ebi.ac.uk/pdbsum/1jca PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1jca ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 15:		Line 16:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jc/1jca_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jc/1jca_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 30:		Line 31:
	</div>		</div>
	<div class="pdbe-citations 1jca" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1jca" style="background-color:#fffaf0;"></div>

	~~==See Also==~~
	*[[Molecular Playground/Insulin\|Molecular Playground/Insulin]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 09:27, 7 February 2016

2016-02-07T09:27:50Z

← Older revision		Revision as of 09:27, 7 February 2016
Line 19:		Line 19:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</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/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].		</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=1jca ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 00:03, 10 September 2015

2015-09-10T00:03:08Z

← Older revision		Revision as of 00:03, 10 September 2015
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	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1j73\|1j73]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1j73\|1j73]]</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=1jca FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jca OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1jca RCSB], [http://www.ebi.ac.uk/pdbsum/1jca PDBsum]</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=1jca FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jca OCA], [http://pdbe.org/1jca PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1jca RCSB], [http://www.ebi.ac.uk/pdbsum/1jca PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
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	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
			<div class="pdbe-citations 1jca" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 12:12, 2 January 2015

2015-01-02T12:12:46Z

← Older revision		Revision as of 12:12, 2 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1jca]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JCA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1JCA FirstGlance]. <br>		<table><tr><td colspan='2'>[[1jca]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JCA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1JCA FirstGlance]. <br>
	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1j73\|1j73]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1j73\|1j73]]</td></tr>
	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1jca FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jca OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1jca RCSB], [http://www.ebi.ac.uk/pdbsum/1jca PDBsum]</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=1jca FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jca OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1jca RCSB], [http://www.ebi.ac.uk/pdbsum/1jca PDBsum]</span></td></tr>
	<table>		</table>
	== Disease ==		== Disease ==
	[[http://www.uniprot.org/uniprot/INS_HUMAN INS_HUMAN]] Defects in INS are the cause of familial hyperproinsulinemia (FHPRI) [MIM:[http://omim.org/entry/176730 176730]].<ref>PMID:3470784</ref> <ref>PMID:2196279</ref> <ref>PMID:4019786</ref> <ref>PMID:1601997</ref> Defects in INS are a cause of diabetes mellitus insulin-dependent type 2 (IDDM2) [MIM:[http://omim.org/entry/125852 125852]]. IDDM2 is a multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.<ref>PMID:18192540</ref> Defects in INS are a cause of diabetes mellitus permanent neonatal (PNDM) [MIM:[http://omim.org/entry/606176 606176]]. PNDM is a rare form of diabetes distinct from childhood-onset autoimmune diabetes mellitus type 1. It is characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Permanent neonatal diabetes requires lifelong therapy.<ref>PMID:17855560</ref> <ref>PMID:18162506</ref> Defects in INS are a cause of maturity-onset diabetes of the young type 10 (MODY10) [MIM:[http://omim.org/entry/613370 613370]]. MODY10 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:18192540</ref> <ref>PMID:18162506</ref> <ref>PMID:20226046</ref>		[[http://www.uniprot.org/uniprot/INS_HUMAN INS_HUMAN]] Defects in INS are the cause of familial hyperproinsulinemia (FHPRI) [MIM:[http://omim.org/entry/176730 176730]].<ref>PMID:3470784</ref> <ref>PMID:2196279</ref> <ref>PMID:4019786</ref> <ref>PMID:1601997</ref> Defects in INS are a cause of diabetes mellitus insulin-dependent type 2 (IDDM2) [MIM:[http://omim.org/entry/125852 125852]]. IDDM2 is a multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.<ref>PMID:18192540</ref> Defects in INS are a cause of diabetes mellitus permanent neonatal (PNDM) [MIM:[http://omim.org/entry/606176 606176]]. PNDM is a rare form of diabetes distinct from childhood-onset autoimmune diabetes mellitus type 1. It is characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Permanent neonatal diabetes requires lifelong therapy.<ref>PMID:17855560</ref> <ref>PMID:18162506</ref> Defects in INS are a cause of maturity-onset diabetes of the young type 10 (MODY10) [MIM:[http://omim.org/entry/613370 613370]]. MODY10 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:18192540</ref> <ref>PMID:18162506</ref> <ref>PMID:20226046</ref>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Burke, G T.]]		[[Category: Burke, G T]]
	[[Category: Chu, Y C.]]		[[Category: Chu, Y C]]
	[[Category: Hellmich, R.]]		[[Category: Hellmich, R]]
	[[Category: Jia, W.]]		[[Category: Jia, W]]
	[[Category: Katsoyannis, P G.]]		[[Category: Katsoyannis, P G]]
	[[Category: Nakagawa, S H.]]		[[Category: Nakagawa, S H]]
	[[Category: Wan, Z.]]		[[Category: Wan, Z]]
	[[Category: Weiss, M A.]]		[[Category: Weiss, M A]]
	[[Category: Zhao, M.]]		[[Category: Zhao, M]]
	[[Category: A8-lysine human insulin]]		[[Category: A8-lysine human insulin]]
	[[Category: Hormone-growth factor complex]]		[[Category: Hormone-growth factor complex]]
	[[Category: Insulin receptor]]		[[Category: Insulin receptor]]

OCA at 15:41, 29 September 2014

2014-09-29T15:41:13Z

← Older revision		Revision as of 15:41, 29 September 2014
Line 1:		Line 1:
	~~{{STRUCTURE_1jca\| PDB=1jca \| SCENE= }}~~		==Non-standard Design of Unstable Insulin Analogues with Enhanced Activity==
	===Non-standard Design of Unstable Insulin Analogues with Enhanced Activity===		<StructureSection load='1jca' size='340' side='right' caption='[[1jca]], [[Resolution\|resolution]] 2.50Å' scene=''>
	~~{{ABSTRACT_PUBMED_11779231}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[1jca]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JCA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1JCA FirstGlance]. <br>
	==Disease==		</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>
	[[http://www.uniprot.org/uniprot/INS_HUMAN INS_HUMAN]] Defects in INS are the cause of familial hyperproinsulinemia (FHPRI) [MIM:[http://omim.org/entry/176730 176730]].<ref>PMID:3470784</ref><ref>PMID:2196279</ref><ref>PMID:4019786</ref><ref>PMID:1601997</ref> Defects in INS are a cause of diabetes mellitus insulin-dependent type 2 (IDDM2) [MIM:[http://omim.org/entry/125852 125852]]. IDDM2 is a multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.<ref>PMID:18192540</ref> Defects in INS are a cause of diabetes mellitus permanent neonatal (PNDM) [MIM:[http://omim.org/entry/606176 606176]]. PNDM is a rare form of diabetes distinct from childhood-onset autoimmune diabetes mellitus type 1. It is characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Permanent neonatal diabetes requires lifelong therapy.<ref>PMID:17855560</ref><ref>PMID:18162506</ref> Defects in INS are a cause of maturity-onset diabetes of the young type 10 (MODY10) [MIM:[http://omim.org/entry/613370 613370]]. MODY10 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:18192540</ref><ref>PMID:18162506</ref><ref>PMID:20226046</ref>		<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1j73\|1j73]]</td></tr>
			<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1jca FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jca OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1jca RCSB], [http://www.ebi.ac.uk/pdbsum/1jca PDBsum]</span></td></tr>
			<table>
			== Disease ==
			[[http://www.uniprot.org/uniprot/INS_HUMAN INS_HUMAN]] Defects in INS are the cause of familial hyperproinsulinemia (FHPRI) [MIM:[http://omim.org/entry/176730 176730]].<ref>PMID:3470784</ref> <ref>PMID:2196279</ref> <ref>PMID:4019786</ref> <ref>PMID:1601997</ref> Defects in INS are a cause of diabetes mellitus insulin-dependent type 2 (IDDM2) [MIM:[http://omim.org/entry/125852 125852]]. IDDM2 is a multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.<ref>PMID:18192540</ref> Defects in INS are a cause of diabetes mellitus permanent neonatal (PNDM) [MIM:[http://omim.org/entry/606176 606176]]. PNDM is a rare form of diabetes distinct from childhood-onset autoimmune diabetes mellitus type 1. It is characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Permanent neonatal diabetes requires lifelong therapy.<ref>PMID:17855560</ref> <ref>PMID:18162506</ref> Defects in INS are a cause of maturity-onset diabetes of the young type 10 (MODY10) [MIM:[http://omim.org/entry/613370 613370]]. MODY10 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:18192540</ref> <ref>PMID:18162506</ref> <ref>PMID:20226046</ref>
			== Function ==
			[[http://www.uniprot.org/uniprot/INS_HUMAN INS_HUMAN]] Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver.
			== 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/jc/1jca_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/chain_selection.php?pdb_ID=2ata ConSurf].
			<div style="clear:both"></div>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			The design of insulin analogues has emphasized stabilization or destabilization of structural elements according to established principles of protein folding. To this end, solvent-exposed side-chains extrinsic to the receptor-binding surface provide convenient sites of modification. An example is provided by an unfavorable helical C-cap (Thr(A8)) whose substitution by favorable amino acids (His(A8) or Arg(A8)) has yielded analogues of improved stability. Remarkably, these analogues also exhibit enhanced activity, suggesting that activity may correlate with stability. Here, we test this hypothesis by substitution of diaminobutyric acid (Dab(A8)), like threonine an amino acid of low helical propensity. The crystal structure of Dab(A8)-insulin is similar to those of native insulin and the related analogue Lys(A8)-insulin. Although no more stable than native insulin, the non-standard analogue is twice as active. Stability and affinity can therefore be uncoupled. To investigate alternative mechanisms by which A8 substitutions enhance activity, multiple substitutions were introduced. Surprisingly, diverse aliphatic, aromatic and polar side-chains enhance receptor binding and biological activity. Because no relationship is observed between activity and helical propensity, we propose that local interactions between the A8 side-chain and an edge of the hormone-receptor interface modulate affinity. Dab(A8)-insulin illustrates the utility of non-standard amino acids in hypothesis-driven protein design.

	~~==Function==~~		Non-standard insulin design: structure-activity relationships at the periphery of the insulin receptor.,Weiss MA, Wan Z, Zhao M, Chu YC, Nakagawa SH, Burke GT, Jia W, Hellmich R, Katsoyannis PG J Mol Biol. 2002 Jan 11;315(2):103-11. PMID:11779231<ref>PMID:11779231</ref>
	~~[[http~~:~~//www~~.~~uniprot.org/uniprot/INS_HUMAN INS_HUMAN]] Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides~~, ~~amino acids and fatty acids. It accelerates glycolysis~~, ~~the pentose phosphate cycle~~, ~~and glycogen synthesis in liver~~.

	~~==About this Structure==~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~[[1jca]] is~~ a ~~4 chain structure. Full crystallographic information is available from [http://oca~~.~~weizmann~~.ac.~~il/oca-bin~~/~~ocashort?id=1JCA OCA].~~		</div>

	==See Also==		==See Also==
	*[[Molecular Playground/Insulin\|Molecular Playground/Insulin]]		*[[Molecular Playground/Insulin\|Molecular Playground/Insulin]]
			== References ==
	==~~Reference~~==		<references/>
	~~<ref group="xtra">PMID:011779231</ref>~~<references ~~group="xtra"~~/><~~references~~/>		__TOC__
			</StructureSection>
	[[Category: Burke, G T.]]		[[Category: Burke, G T.]]
	[[Category: Chu, Y C.]]		[[Category: Chu, Y C.]]

OCA at 17:47, 24 March 2013

2013-03-24T17:47:22Z

← Older revision		Revision as of 17:47, 24 March 2013
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	~~[[Image:1jca.png\|left\|200px]]~~

	{{STRUCTURE_1jca\| PDB=1jca \| SCENE= }}		{{STRUCTURE_1jca\| PDB=1jca \| SCENE= }}
			===Non-standard Design of Unstable Insulin Analogues with Enhanced Activity===
			{{ABSTRACT_PUBMED_11779231}}

	===~~Non~~-~~standard Design~~ of ~~Unstable Insulin Analogues with Enhanced Activity===~~		==Disease==
			[[http://www.uniprot.org/uniprot/INS_HUMAN INS_HUMAN]] Defects in INS are the cause of familial hyperproinsulinemia (FHPRI) [MIM:[http://omim.org/entry/176730 176730]].<ref>PMID:3470784</ref><ref>PMID:2196279</ref><ref>PMID:4019786</ref><ref>PMID:1601997</ref> Defects in INS are a cause of diabetes mellitus insulin-dependent type 2 (IDDM2) [MIM:[http://omim.org/entry/125852 125852]]. IDDM2 is a multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.<ref>PMID:18192540</ref> Defects in INS are a cause of diabetes mellitus permanent neonatal (PNDM) [MIM:[http://omim.org/entry/606176 606176]]. PNDM is a rare form of diabetes distinct from childhood-onset autoimmune diabetes mellitus type 1. It is characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Permanent neonatal diabetes requires lifelong therapy.<ref>PMID:17855560</ref><ref>PMID:18162506</ref> Defects in INS are a cause of maturity-onset diabetes of the young type 10 (MODY10) [MIM:[http://omim.org/entry/613370 613370]]. MODY10 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:18192540</ref><ref>PMID:18162506</ref><ref>PMID:20226046</ref>

	~~{{ABSTRACT_PUBMED_11779231}}~~		==Function==
			[[http://www.uniprot.org/uniprot/INS_HUMAN INS_HUMAN]] Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver.

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

	==Reference==		==Reference==
	<ref group="xtra">PMID:011779231</ref><references group="xtra"/>		<ref group="xtra">PMID:011779231</ref><references group="xtra"/><references/>
	[[Category: Burke, G T.]]		[[Category: Burke, G T.]]
	[[Category: Chu, Y C.]]		[[Category: Chu, Y C.]]

← Older revision		Revision as of 06:38, 11 August 2021
Line 3:		Line 3:
	<StructureSection load='1jca' size='340' side='right'caption='[[1jca]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='1jca' size='340' side='right'caption='[[1jca]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1jca]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JCA OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1JCA FirstGlance]. <br>		<table><tr><td colspan='2'>[[1jca]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JCA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JCA FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1j73\|1j73]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1j73\|1j73]]</div></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=1jca FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jca OCA], [~~http~~://pdbe.org/1jca PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1jca RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1jca PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1jca 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=1jca FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jca OCA], [https://pdbe.org/1jca PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1jca RCSB], [https://www.ebi.ac.uk/pdbsum/1jca PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1jca ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[~~http~~://www.uniprot.org/uniprot/INS_HUMAN INS_HUMAN]] Defects in INS are the cause of familial hyperproinsulinemia (FHPRI) [MIM:[~~http~~://omim.org/entry/176730 176730]].<ref>PMID:3470784</ref> <ref>PMID:2196279</ref> <ref>PMID:4019786</ref> <ref>PMID:1601997</ref> Defects in INS are a cause of diabetes mellitus insulin-dependent type 2 (IDDM2) [MIM:[~~http~~://omim.org/entry/125852 125852]]. IDDM2 is a multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.<ref>PMID:18192540</ref> Defects in INS are a cause of diabetes mellitus permanent neonatal (PNDM) [MIM:[~~http~~://omim.org/entry/606176 606176]]. PNDM is a rare form of diabetes distinct from childhood-onset autoimmune diabetes mellitus type 1. It is characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Permanent neonatal diabetes requires lifelong therapy.<ref>PMID:17855560</ref> <ref>PMID:18162506</ref> Defects in INS are a cause of maturity-onset diabetes of the young type 10 (MODY10) [MIM:[~~http~~://omim.org/entry/613370 613370]]. MODY10 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:18192540</ref> <ref>PMID:18162506</ref> <ref>PMID:20226046</ref>		[[https://www.uniprot.org/uniprot/INS_HUMAN INS_HUMAN]] Defects in INS are the cause of familial hyperproinsulinemia (FHPRI) [MIM:[https://omim.org/entry/176730 176730]].<ref>PMID:3470784</ref> <ref>PMID:2196279</ref> <ref>PMID:4019786</ref> <ref>PMID:1601997</ref> Defects in INS are a cause of diabetes mellitus insulin-dependent type 2 (IDDM2) [MIM:[https://omim.org/entry/125852 125852]]. IDDM2 is a multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.<ref>PMID:18192540</ref> Defects in INS are a cause of diabetes mellitus permanent neonatal (PNDM) [MIM:[https://omim.org/entry/606176 606176]]. PNDM is a rare form of diabetes distinct from childhood-onset autoimmune diabetes mellitus type 1. It is characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Permanent neonatal diabetes requires lifelong therapy.<ref>PMID:17855560</ref> <ref>PMID:18162506</ref> Defects in INS are a cause of maturity-onset diabetes of the young type 10 (MODY10) [MIM:[https://omim.org/entry/613370 613370]]. MODY10 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:18192540</ref> <ref>PMID:18162506</ref> <ref>PMID:20226046</ref>
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/INS_HUMAN INS_HUMAN]] Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver.		[[https://www.uniprot.org/uniprot/INS_HUMAN INS_HUMAN]] Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]