1t1q - Revision history

OCA at 08:37, 1 May 2024

OCA — Wed, 01 May 2024 08:37:36 GMT

←Older revision		Revision as of 08:37, 1 May 2024
Line 1:		Line 1:

	==NMR STRUCTURE OF HUMAN INSULIN MUTANT HIS-B10-ASP, VAL-B12-ABA, PRO-B28-LYS, LYS-B29-PRO, 15 STRUCTURES==		==NMR STRUCTURE OF HUMAN INSULIN MUTANT HIS-B10-ASP, VAL-B12-ABA, PRO-B28-LYS, LYS-B29-PRO, 15 STRUCTURES==
-	<StructureSection load='1t1q' size='340' side='right'caption='[[1t1q~~]], [[NMR_Ensembles_of_Models \| 15 NMR models~~]]' scene=''>	+	<StructureSection load='1t1q' size='340' side='right'caption='[[1t1q]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1t1q]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T1Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1T1Q FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1t1q]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T1Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1T1Q FirstGlance]. <br>
-	</td></tr><tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"~~><scene name~~=~~'pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene~~></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"><~~div style~~='~~overflow~~: ~~auto; max~~-~~height: 3em;~~'>~~[[1lnp\|1lnp]], [[1t1k\|1t1k]], [[1t1p\|1t1p]]~~</~~div~~></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</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=1t1q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t1q OCA], [https://pdbe.org/1t1q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1t1q RCSB], [https://www.ebi.ac.uk/pdbsum/1t1q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1t1q 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=1t1q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t1q OCA], [https://pdbe.org/1t1q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1t1q RCSB], [https://www.ebi.ac.uk/pdbsum/1t1q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1t1q 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]]
Line 22:		Line 22:
	</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=1t1q 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=1t1q ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Binding of insulin to the insulin receptor plays a central role in the hormonal control of metabolism. Here, we investigate possible contact sites between the receptor and the conserved non-polar surface of the B-chain. Evidence is presented that two contiguous sites in an alpha-helix, Val(B12) and Tyr(B16), contact the receptor. Chemical synthesis is exploited to obtain non-standard substitutions in an engineered monomer (DKP-insulin). Substitution of Tyr(B16) by an isosteric photo-activatable derivative (para-azido-phenylalanine) enables efficient cross-linking to the receptor. Such cross-linking is specific and maps to the L1 beta-helix of the alpha-subunit. Because substitution of Val(B12) by larger side-chains markedly impairs receptor binding, cross-linking studies at B12 were not undertaken. Structure-function relationships are instead probed by side-chains of similar or smaller volume: respective substitution of Val(B12) by alanine, threonine, and alpha-aminobutyric acid leads to activities of 1(+/-0.1)%, 13(+/-6)%, and 14(+/-5)% (relative to DKP-insulin) without disproportionate changes in negative cooperativity. NMR structures are essentially identical with native insulin. The absence of transmitted structural changes suggests that the low activities of B12 analogues reflect local perturbation of a "high-affinity" hormone-receptor contact. By contrast, because position B16 tolerates alanine substitution (relative activity 34(+/-10)%), the contribution of this neighboring interaction is smaller. Together, our results support a model in which the B-chain alpha-helix, functioning as an essential recognition element, docks against the L1 beta-helix of the insulin receptor.
-
-	How insulin binds: the B-chain alpha-helix contacts the L1 beta-helix of the insulin receptor.,Huang K, Xu B, Hu SQ, Chu YC, Hua QX, Qu Y, Li B, Wang S, Wang RY, Nakagawa SH, Theede AM, Whittaker J, De Meyts P, Katsoyannis PG, Weiss MA J Mol Biol. 2004 Aug 6;341(2):529-50. PMID:15276842<ref>PMID:15276842</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 1t1q" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 38:		Line 29:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Chu~~, Y C~~]]	+	[[Category: Chu YC]]
-	[[Category: ~~Hu, S Q~~]]	+	[[Category: De Meyts P]]
-	[[Category: ~~Hua, Q X~~]]	+	[[Category: Hu SQ]]
-	[[Category: ~~Huang, K~~]]	+	[[Category: Hua QX]]
-	[[Category: ~~Katsoyannis, P G~~]]	+	[[Category: Huang K]]
-	[[Category: ~~Meyts, P De~~]]	+	[[Category: Katsoyannis PG]]
-	[[Category: Nakagawa~~, S H~~]]	+	[[Category: Nakagawa SH]]
-	[[Category: Weiss~~, M A~~]]	+	[[Category: Weiss MA]]
-	[[Category: Whittaker, J]]	+	[[Category: Whittaker J]]
-	[[Category: Xu, B]]	+	[[Category: Xu B]]
-	~~[[Category: Aba-b12-dkp-insulin]]~~	+
-	~~[[Category: Hormone-growth factor complex]]~~	+
-	~~[[Category: Insulin receptor]]~~	+
-	~~[[Category: Protein unfolding]]~~	+
-	~~[[Category: Receptor binding~~]]	+

OCA at 07:40, 22 September 2021

OCA — Wed, 22 Sep 2021 07:40:35 GMT

OCA at 14:21, 18 December 2019

OCA — Wed, 18 Dec 2019 14:21:02 GMT

←Older revision		Revision as of 14:21, 18 December 2019
Line 1:		Line 1:

	==NMR STRUCTURE OF HUMAN INSULIN MUTANT HIS-B10-ASP, VAL-B12-ABA, PRO-B28-LYS, LYS-B29-PRO, 15 STRUCTURES==		==NMR STRUCTURE OF HUMAN INSULIN MUTANT HIS-B10-ASP, VAL-B12-ABA, PRO-B28-LYS, LYS-B29-PRO, 15 STRUCTURES==
-	<StructureSection load='1t1q' size='340' side='right' caption='[[1t1q]], [[NMR_Ensembles_of_Models \| 15 NMR models]]' scene=''>	+	<StructureSection load='1t1q' size='340' side='right'caption='[[1t1q]], [[NMR_Ensembles_of_Models \| 15 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1t1q]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T1Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1T1Q FirstGlance]. <br>		<table><tr><td colspan='2'>[[1t1q]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T1Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1T1Q FirstGlance]. <br>
Line 33:		Line 33:

	==See Also==		==See Also==
-	*[[~~Molecular Playground/~~Insulin\|~~Molecular Playground/~~Insulin]]	+	*[[Insulin 3D Structures\|Insulin 3D Structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Chu, Y C]]		[[Category: Chu, Y C]]
	[[Category: Hu, S Q]]		[[Category: Hu, S Q]]

OCA at 08:00, 14 March 2018

OCA — Wed, 14 Mar 2018 08:00:42 GMT

←Older revision		Revision as of 08:00, 14 March 2018
Line 1:		Line 1:
		+
	==NMR STRUCTURE OF HUMAN INSULIN MUTANT HIS-B10-ASP, VAL-B12-ABA, PRO-B28-LYS, LYS-B29-PRO, 15 STRUCTURES==		==NMR STRUCTURE OF HUMAN INSULIN MUTANT HIS-B10-ASP, VAL-B12-ABA, PRO-B28-LYS, LYS-B29-PRO, 15 STRUCTURES==
	<StructureSection load='1t1q' size='340' side='right' caption='[[1t1q]], [[NMR_Ensembles_of_Models \| 15 NMR models]]' scene=''>		<StructureSection load='1t1q' size='340' side='right' caption='[[1t1q]], [[NMR_Ensembles_of_Models \| 15 NMR models]]' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene></td></tr>		</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1lnp\|1lnp]], [[1t1k\|1t1k]], [[1t1p\|1t1p]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1lnp\|1lnp]], [[1t1k\|1t1k]], [[1t1p\|1t1p]]</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=1t1q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t1q OCA], [http://pdbe.org/1t1q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1t1q RCSB], [http://www.ebi.ac.uk/pdbsum/1t1q 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=1t1q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t1q OCA], [http://pdbe.org/1t1q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1t1q RCSB], [http://www.ebi.ac.uk/pdbsum/1t1q PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1t1q ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
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	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/t1/1t1q_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/t1/1t1q_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>
	</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=1t1q ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 13:20, 11 September 2015

OCA — Fri, 11 Sep 2015 13:20:04 GMT

←Older revision		Revision as of 13:20, 11 September 2015
Line 5:		Line 5:
	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene></td></tr>		</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1lnp\|1lnp]], [[1t1k\|1t1k]], [[1t1p\|1t1p]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1lnp\|1lnp]], [[1t1k\|1t1k]], [[1t1p\|1t1p]]</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=1t1q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t1q OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1t1q RCSB], [http://www.ebi.ac.uk/pdbsum/1t1q 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=1t1q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t1q OCA], [http://pdbe.org/1t1q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1t1q RCSB], [http://www.ebi.ac.uk/pdbsum/1t1q PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 29:		Line 29:
	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 1t1q" style="background-color:#fffaf0;"></div>

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

OCA at 08:24, 6 January 2015

OCA — Tue, 06 Jan 2015 08:24:07 GMT

←Older revision		Revision as of 08:24, 6 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1t1q]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T1Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1T1Q FirstGlance]. <br>		<table><tr><td colspan='2'>[[1t1q]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T1Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1T1Q FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene></td></tr>	+	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1lnp\|1lnp]], [[1t1k\|1t1k]], [[1t1p\|1t1p]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1lnp\|1lnp]], [[1t1k\|1t1k]], [[1t1p\|1t1p]]</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=1t1q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t1q OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1t1q RCSB], [http://www.ebi.ac.uk/pdbsum/1t1q 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=1t1q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t1q OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1t1q RCSB], [http://www.ebi.ac.uk/pdbsum/1t1q 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>
Line 36:		Line 36:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Chu, Y C.]]	+	[[Category: Chu, Y C]]
-	[[Category: Hu, S Q.]]	+	[[Category: Hu, S Q]]
-	[[Category: Hua, Q X.]]	+	[[Category: Hua, Q X]]
-	[[Category: Huang, K.]]	+	[[Category: Huang, K]]
-	[[Category: Katsoyannis, P G.]]	+	[[Category: Katsoyannis, P G]]
-	[[Category: Meyts, P De.]]	+	[[Category: Meyts, P De]]
-	[[Category: Nakagawa, S H.]]	+	[[Category: Nakagawa, S H]]
-	[[Category: Weiss, M A.]]	+	[[Category: Weiss, M A]]
-	[[Category: Whittaker, J.]]	+	[[Category: Whittaker, J]]
-	[[Category: Xu, B.]]	+	[[Category: Xu, B]]
	[[Category: Aba-b12-dkp-insulin]]		[[Category: Aba-b12-dkp-insulin]]
	[[Category: Hormone-growth factor complex]]		[[Category: Hormone-growth factor complex]]

OCA at 15:44, 29 September 2014

OCA — Mon, 29 Sep 2014 15:44:31 GMT

←Older revision		Revision as of 15:44, 29 September 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_1t1q\| PDB=1t1q \| SCENE= }}~~	+	==NMR STRUCTURE OF HUMAN INSULIN MUTANT HIS-B10-ASP, VAL-B12-ABA, PRO-B28-LYS, LYS-B29-PRO, 15 STRUCTURES==
-	===NMR STRUCTURE OF HUMAN INSULIN MUTANT HIS-B10-ASP, VAL-B12-ABA, PRO-B28-LYS, LYS-B29-PRO, 15 STRUCTURES===	+	<StructureSection load='1t1q' size='340' side='right' caption='[[1t1q]], [[NMR_Ensembles_of_Models \| 15 NMR models]]' scene=''>
-	~~{{ABSTRACT_PUBMED_15276842}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1t1q]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T1Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1T1Q FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene></td></tr>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1lnp\|1lnp]], [[1t1k\|1t1k]], [[1t1p\|1t1p]]</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=1t1q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t1q OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1t1q RCSB], [http://www.ebi.ac.uk/pdbsum/1t1q 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/t1/1t1q_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 ==
		+	Binding of insulin to the insulin receptor plays a central role in the hormonal control of metabolism. Here, we investigate possible contact sites between the receptor and the conserved non-polar surface of the B-chain. Evidence is presented that two contiguous sites in an alpha-helix, Val(B12) and Tyr(B16), contact the receptor. Chemical synthesis is exploited to obtain non-standard substitutions in an engineered monomer (DKP-insulin). Substitution of Tyr(B16) by an isosteric photo-activatable derivative (para-azido-phenylalanine) enables efficient cross-linking to the receptor. Such cross-linking is specific and maps to the L1 beta-helix of the alpha-subunit. Because substitution of Val(B12) by larger side-chains markedly impairs receptor binding, cross-linking studies at B12 were not undertaken. Structure-function relationships are instead probed by side-chains of similar or smaller volume: respective substitution of Val(B12) by alanine, threonine, and alpha-aminobutyric acid leads to activities of 1(+/-0.1)%, 13(+/-6)%, and 14(+/-5)% (relative to DKP-insulin) without disproportionate changes in negative cooperativity. NMR structures are essentially identical with native insulin. The absence of transmitted structural changes suggests that the low activities of B12 analogues reflect local perturbation of a "high-affinity" hormone-receptor contact. By contrast, because position B16 tolerates alanine substitution (relative activity 34(+/-10)%), the contribution of this neighboring interaction is smaller. Together, our results support a model in which the B-chain alpha-helix, functioning as an essential recognition element, docks against the L1 beta-helix of the insulin receptor.

-	~~==Disease==~~	+	How insulin binds: the B-chain alpha-helix contacts the L1 beta-helix of the insulin receptor.,Huang K, Xu B, Hu SQ, Chu YC, Hua QX, Qu Y, Li B, Wang S, Wang RY, Nakagawa SH, Theede AM, Whittaker J, De Meyts P, Katsoyannis PG, Weiss MA J Mol Biol. 2004 Aug 6;341(2):529-50. PMID:15276842<ref>PMID:15276842</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>	+

-	~~==Function==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[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~~.	+	</div>
-		+
-	~~==About this Structure==~~	+
-	~~[[1t1q]] is a 2 chain structure~~. ~~Full experimental information is available from [http://oca~~.~~weizmann.ac.il~~/~~oca-bin/ocashort?id=1T1Q OCA].~~	+

	==See Also==		==See Also==
	*[[Molecular Playground/Insulin\|Molecular Playground/Insulin]]		*[[Molecular Playground/Insulin\|Molecular Playground/Insulin]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:015276842</ref><ref group="xtra">PMID:011123908</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Chu, Y C.]]		[[Category: Chu, Y C.]]
	[[Category: Hu, S Q.]]		[[Category: Hu, S Q.]]

OCA at 17:53, 24 March 2013

OCA — Sun, 24 Mar 2013 17:53:07 GMT

←Older revision		Revision as of 17:53, 24 March 2013
Line 1:		Line 1:
-	[[Image:1t1q.png\|left\|200px]]
-
	{{STRUCTURE_1t1q\| PDB=1t1q \| SCENE= }}		{{STRUCTURE_1t1q\| PDB=1t1q \| SCENE= }}
-
	===NMR STRUCTURE OF HUMAN INSULIN MUTANT HIS-B10-ASP, VAL-B12-ABA, PRO-B28-LYS, LYS-B29-PRO, 15 STRUCTURES===		===NMR STRUCTURE OF HUMAN INSULIN MUTANT HIS-B10-ASP, VAL-B12-ABA, PRO-B28-LYS, LYS-B29-PRO, 15 STRUCTURES===
		+	{{ABSTRACT_PUBMED_15276842}}

-	~~{{ABSTRACT_PUBMED_15276842}}~~	+	==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.

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

	==Reference==		==Reference==
-	<ref group="xtra">PMID:015276842</ref><ref group="xtra">PMID:011123908</ref><references group="xtra"/>	+	<ref group="xtra">PMID:015276842</ref><ref group="xtra">PMID:011123908</ref><references group="xtra"/><references/>
	[[Category: Chu, Y C.]]		[[Category: Chu, Y C.]]
	[[Category: Hu, S Q.]]		[[Category: Hu, S Q.]]

OCA at 19:11, 20 October 2012

OCA — Sat, 20 Oct 2012 19:11:09 GMT

←Older revision		Revision as of 19:11, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[1t1q]] is a 2 chain structure ~~of [[Molecular Playground/Insulin]]~~. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T1Q OCA].	+	[[1t1q]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T1Q OCA].

	==See Also==		==See Also==
Line 14:		Line 14:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:015276842</ref><ref group="xtra">PMID:011123908~~</ref><ref group="xtra">PMID:009148904</ref><ref group="xtra">PMID:008876979</ref><ref group="xtra">PMID:008448120</ref><ref group="xtra">PMID:007014485~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:015276842</ref><ref group="xtra">PMID:011123908</ref><references group="xtra"/>
	[[Category: Chu, Y C.]]		[[Category: Chu, Y C.]]
	[[Category: Hu, S Q.]]		[[Category: Hu, S Q.]]

OCA at 06:33, 27 July 2012

OCA — Fri, 27 Jul 2012 06:33:15 GMT

←Older revision		Revision as of 06:33, 27 July 2012
Line 1:		Line 1:
	[[Image:1t1q.png\|left\|200px]]		[[Image:1t1q.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_1t1q", 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_1t1q\| PDB=1t1q \| SCENE= }}		{{STRUCTURE_1t1q\| PDB=1t1q \| SCENE= }}

	===NMR STRUCTURE OF HUMAN INSULIN MUTANT HIS-B10-ASP, VAL-B12-ABA, PRO-B28-LYS, LYS-B29-PRO, 15 STRUCTURES===		===NMR STRUCTURE OF HUMAN INSULIN MUTANT HIS-B10-ASP, VAL-B12-ABA, PRO-B28-LYS, LYS-B29-PRO, 15 STRUCTURES===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_15276842}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 15276842 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_15276842}}		{{ABSTRACT_PUBMED_15276842}}

Line 22:		Line 11:

	==See Also==		==See Also==
-	*[[Molecular Playground/Insulin]]	+	*[[Molecular Playground/Insulin\|Molecular Playground/Insulin]]

	==Reference==		==Reference==

←Older revision		Revision as of 07:40, 22 September 2021
Line 3:		Line 3:
	<StructureSection load='1t1q' size='340' side='right'caption='[[1t1q]], [[NMR_Ensembles_of_Models \| 15 NMR models]]' scene=''>		<StructureSection load='1t1q' size='340' side='right'caption='[[1t1q]], [[NMR_Ensembles_of_Models \| 15 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1t1q]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T1Q OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1T1Q FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1t1q]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T1Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1T1Q FirstGlance]. <br>
	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene></td></tr>		</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1lnp\|1lnp]], [[1t1k\|1t1k]], [[1t1p\|1t1p]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1lnp\|1lnp]], [[1t1k\|1t1k]], [[1t1p\|1t1p]]</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=1t1q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t1q OCA], [~~http~~://pdbe.org/1t1q PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1t1q RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1t1q PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1t1q 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=1t1q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t1q OCA], [https://pdbe.org/1t1q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1t1q RCSB], [https://www.ebi.ac.uk/pdbsum/1t1q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1t1q 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]]