3p2x - Revision history

OCA at 09:47, 6 September 2023

2023-09-06T09:47:37Z

←Older revision		Revision as of 09:47, 6 September 2023
Line 3:		Line 3:
	<StructureSection load='3p2x' size='340' side='right'caption='[[3p2x]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='3p2x' size='340' side='right'caption='[[3p2x]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3p2x]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P2X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3P2X FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3p2x]] 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=3P2X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3P2X FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>~~, ~~<scene name='pdbligand=IPH:PHENOL'>IPH</scene>, <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]] 2Å</td></tr>
-	<tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"><scene name='pdbligand=DAL:D-ALANINE'>DAL</scene><~~/td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=IPH:PHENOL'>IPH</scene>, <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"><div style~~=~~'overflow~~: ~~auto; max-height: 3em;~~'>~~[[3jsd\|3jsd]], [[3p33\|3p33]]~~</~~div~~></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=3p2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p2x OCA], [https://pdbe.org/3p2x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3p2x RCSB], [https://www.ebi.ac.uk/pdbsum/3p2x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3p2x 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=3p2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p2x OCA], [https://pdbe.org/3p2x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3p2x RCSB], [https://www.ebi.ac.uk/pdbsum/3p2x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3p2x 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.
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Naturally occurring mutations in insulin associated with diabetes mellitus identify critical determinants of its biological activity. Here, we describe the crystal structure of insulin Wakayama, a clinical variant in which a conserved valine in the A chain (residue A3) is substituted by leucine. The substitution occurs within a crevice adjoining the classical receptor-binding surface and impairs receptor binding by 500-fold, an unusually severe decrement among mutant insulins. To resolve whether such decreased activity is directly or indirectly mediated by the variant side chain, we have determined the crystal structure of Leu(A3)-insulin and investigated the photo-cross-linking properties of an A3 analogue containing p-azidophenylalanine. The structure, characterized in a novel crystal form as an R(6) zinc hexamer at 2.3 A resolution, is essentially identical to that of the wild-type R(6) hexamer. The variant side chain remains buried in a nativelike crevice with small adjustments in surrounding side chains. The corresponding photoactivatable analogue, although of low affinity, exhibits efficient cross-linking to the insulin receptor. The site of photo-cross-linking lies within a 14 kDa C-terminal domain of the alpha-subunit. This domain, unrelated in sequence to the major insulin-binding region in the N-terminal L1 beta-helix, is also contacted by photoactivatable probes at positions A8 and B25. Packing of Val(A3) at this interface may require a conformational change in the B chain to expose the A3-related crevice. The structure of insulin Wakayama thus evokes the reasoning of Sherlock Holmes in "the curious incident of the dog in the night": the apparent absence of structural perturbations (like the dog that did not bark) provides a critical clue to the function of a hidden receptor-binding surface.	+
-		+
-	Diabetes-associated mutations in human insulin: crystal structure and photo-cross-linking studies of a-chain variant insulin Wakayama.,Wan ZL, Huang K, Xu B, Hu SQ, Wang S, Chu YC, Katsoyannis PG, Weiss MA Biochemistry. 2005 Apr 5;44(13):5000-16. PMID:15794638<ref>PMID:15794638</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3p2x" style="background-color:#fffaf0;"></div>~~	+

	==See Also==		==See Also==
Line 29:		Line 19:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Dodson~~, G G~~]]	+	[[Category: Dodson GG]]
-	[[Category: Hu~~, S Q~~]]	+	[[Category: Hu SQ]]
-	[[Category: Hua~~, Q X~~]]	+	[[Category: Hua QX]]
-	[[Category: Huang, K]]	+	[[Category: Huang K]]
-	[[Category: Jia~~, W H~~]]	+	[[Category: Jia WH]]
-	[[Category: Katsoyannis~~, P G~~]]	+	[[Category: Katsoyannis PG]]
-	[[Category: Phillip~~, N F~~]]	+	[[Category: Phillip NF]]
-	[[Category: Wan~~, Z L~~]]	+	[[Category: Wan ZL]]
-	[[Category: Weiss~~, M A~~]]	+	[[Category: Weiss MA]]
-	[[Category: Whittingham, J]]	+	[[Category: Whittingham J]]
-	~~[[Category: Global health]]~~	+
-	~~[[Category: Hormone]]~~	+
-	~~[[Category: Insulin fibrillation]]~~	+
-	~~[[Category: Long-acting insulin analog]]~~	+
-	~~[[Category: Receptor binding protein engineering]]~~	+
-	~~[[Category: Zinc-binding site~~]]	+

OCA at 11:16, 18 May 2022

2022-05-18T11:16:17Z

←Older revision		Revision as of 11:16, 18 May 2022
Line 1:		Line 1:

	==Insulin fibrillation is the Janus face of induced fit. A chiaral clamp stabilizes the native state at the expense of activity==		==Insulin fibrillation is the Janus face of induced fit. A chiaral clamp stabilizes the native state at the expense of activity==
-	<StructureSection load='3p2x' size='340' side='right' caption='[[3p2x]], [[Resolution\|resolution]] 2.00Å' scene=''>	+	<StructureSection load='3p2x' size='340' side='right'caption='[[3p2x]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3p2x]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P2X OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3P2X FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3p2x]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P2X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3P2X FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=IPH:PHENOL'>IPH</scene>, <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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=IPH:PHENOL'>IPH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DAL:D-ALANINE'>DAL</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DAL:D-ALANINE'>DAL</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3jsd\|3jsd]], [[3p33\|3p33]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3jsd\|3jsd]], [[3p33\|3p33]]</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=3p2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p2x OCA], [~~http~~://pdbe.org/3p2x PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3p2x RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3p2x PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3p2x 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=3p2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p2x OCA], [https://pdbe.org/3p2x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3p2x RCSB], [https://www.ebi.ac.uk/pdbsum/3p2x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3p2x 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.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 24:		Line 24:

	==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: Dodson, G G]]		[[Category: Dodson, G G]]
	[[Category: Hu, S Q]]		[[Category: Hu, S Q]]

OCA at 18:02, 11 August 2016

2016-08-11T18:02:07Z

←Older revision		Revision as of 18:02, 11 August 2016
Line 1:		Line 1:
		+
	==Insulin fibrillation is the Janus face of induced fit. A chiaral clamp stabilizes the native state at the expense of activity==		==Insulin fibrillation is the Janus face of induced fit. A chiaral clamp stabilizes the native state at the expense of activity==
	<StructureSection load='3p2x' size='340' side='right' caption='[[3p2x]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='3p2x' size='340' side='right' caption='[[3p2x]], [[Resolution\|resolution]] 2.00Å' scene=''>
Line 6:		Line 7:
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DAL:D-ALANINE'>DAL</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DAL:D-ALANINE'>DAL</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3jsd\|3jsd]], [[3p33\|3p33]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3jsd\|3jsd]], [[3p33\|3p33]]</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=3p2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p2x OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3p2x RCSB], [http://www.ebi.ac.uk/pdbsum/3p2x 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=3p2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p2x OCA], [http://pdbe.org/3p2x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3p2x RCSB], [http://www.ebi.ac.uk/pdbsum/3p2x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3p2x ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 21:
	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 3p2x" style="background-color:#fffaf0;"></div>

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

OCA at 08:21, 25 January 2015

2015-01-25T08:21:22Z

←Older revision		Revision as of 08:21, 25 January 2015
Line 27:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Dodson, G G.]]	+	[[Category: Dodson, G G]]
-	[[Category: Hu, S Q.]]	+	[[Category: Hu, S Q]]
-	[[Category: Hua, Q X.]]	+	[[Category: Hua, Q X]]
-	[[Category: Huang, K.]]	+	[[Category: Huang, K]]
-	[[Category: Jia, W H.]]	+	[[Category: Jia, W H]]
-	[[Category: Katsoyannis, P G.]]	+	[[Category: Katsoyannis, P G]]
-	[[Category: Phillip, N F.]]	+	[[Category: Phillip, N F]]
-	[[Category: Wan, Z L.]]	+	[[Category: Wan, Z L]]
-	[[Category: Weiss, M A.]]	+	[[Category: Weiss, M A]]
-	[[Category: Whittingham, J.]]	+	[[Category: Whittingham, J]]
	[[Category: Global health]]		[[Category: Global health]]
	[[Category: Hormone]]		[[Category: Hormone]]

OCA at 11:31, 22 October 2014

2014-10-22T11:31:10Z

←Older revision		Revision as of 11:31, 22 October 2014
Line 20:		Line 20:
	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>
		+
		+	==See Also==
		+	*[[Molecular Playground/Insulin\|Molecular Playground/Insulin]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:50, 20 October 2014

2014-10-20T08:50:33Z

←Older revision		Revision as of 08:50, 20 October 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3p2x\| PDB=3p2x \| SCENE= }}~~	+	==Insulin fibrillation is the Janus face of induced fit. A chiaral clamp stabilizes the native state at the expense of activity==
-	===Insulin fibrillation is the Janus face of induced fit. A chiaral clamp stabilizes the native state at the expense of activity===	+	<StructureSection load='3p2x' size='340' side='right' caption='[[3p2x]], [[Resolution\|resolution]] 2.00Å' scene=''>
-	~~{{ABSTRACT_PUBMED_15794638}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[3p2x]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P2X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3P2X FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=IPH:PHENOL'>IPH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	[[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 id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DAL:D-ALANINE'>DAL</scene></td></tr>
-		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3jsd\|3jsd]], [[3p33\|3p33]]</td></tr>
-	==Function==	+	<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=3p2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p2x OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3p2x RCSB], [http://www.ebi.ac.uk/pdbsum/3p2x 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.		[[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 style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Naturally occurring mutations in insulin associated with diabetes mellitus identify critical determinants of its biological activity. Here, we describe the crystal structure of insulin Wakayama, a clinical variant in which a conserved valine in the A chain (residue A3) is substituted by leucine. The substitution occurs within a crevice adjoining the classical receptor-binding surface and impairs receptor binding by 500-fold, an unusually severe decrement among mutant insulins. To resolve whether such decreased activity is directly or indirectly mediated by the variant side chain, we have determined the crystal structure of Leu(A3)-insulin and investigated the photo-cross-linking properties of an A3 analogue containing p-azidophenylalanine. The structure, characterized in a novel crystal form as an R(6) zinc hexamer at 2.3 A resolution, is essentially identical to that of the wild-type R(6) hexamer. The variant side chain remains buried in a nativelike crevice with small adjustments in surrounding side chains. The corresponding photoactivatable analogue, although of low affinity, exhibits efficient cross-linking to the insulin receptor. The site of photo-cross-linking lies within a 14 kDa C-terminal domain of the alpha-subunit. This domain, unrelated in sequence to the major insulin-binding region in the N-terminal L1 beta-helix, is also contacted by photoactivatable probes at positions A8 and B25. Packing of Val(A3) at this interface may require a conformational change in the B chain to expose the A3-related crevice. The structure of insulin Wakayama thus evokes the reasoning of Sherlock Holmes in "the curious incident of the dog in the night": the apparent absence of structural perturbations (like the dog that did not bark) provides a critical clue to the function of a hidden receptor-binding surface.

-	~~==About this Structure==~~	+	Diabetes-associated mutations in human insulin: crystal structure and photo-cross-linking studies of a-chain variant insulin Wakayama.,Wan ZL, Huang K, Xu B, Hu SQ, Wang S, Chu YC, Katsoyannis PG, Weiss MA Biochemistry. 2005 Apr 5;44(13):5000-16. PMID:15794638<ref>PMID:15794638</ref>
-	~~[[3p2x]] is~~ a 4 chain ~~structure~~. ~~Full crystallographic information is available from [http://oca~~.~~weizmann.ac.il/oca~~-~~bin/ocashort?id=3P2X OCA]~~.	+
-		+
-	~~==See Also==~~	+
-	*[[Molecular Playground/Insulin\|Molecular Playground/~~Insulin]]~~	+

-	~~==Reference==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~<ref group="xtra">PMID:015794638<~~/~~ref>~~<~~ref group="xtra"~~>~~PMID:014596591~~</~~ref~~>~~<ref group~~=~~"xtra">PMID:015610006</ref><ref group~~=~~"xtra">PMID:002905485</ref><ref group~~=~~"xtra">PMID:002648161</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	</div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Dodson, G G.]]		[[Category: Dodson, G G.]]
	[[Category: Hu, S Q.]]		[[Category: Hu, S Q.]]

OCA at 03:36, 25 March 2013

2013-03-25T03:36:16Z

←Older revision		Revision as of 03:36, 25 March 2013
Line 1:		Line 1:
-	[[Image:3p2x.png\|left\|200px]]
-
	{{STRUCTURE_3p2x\| PDB=3p2x \| SCENE= }}		{{STRUCTURE_3p2x\| PDB=3p2x \| SCENE= }}
-
	===Insulin fibrillation is the Janus face of induced fit. A chiaral clamp stabilizes the native state at the expense of activity===		===Insulin fibrillation is the Janus face of induced fit. A chiaral clamp stabilizes the native state at the expense of activity===
		+	{{ABSTRACT_PUBMED_15794638}}

-	~~{{ABSTRACT_PUBMED_15794638}}~~	+	==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:015794638</ref><ref group="xtra">PMID:014596591</ref><ref group="xtra">PMID:015610006</ref><ref group="xtra">PMID:002905485</ref><ref group="xtra">PMID:002648161</ref><references group="xtra"/>	+	<ref group="xtra">PMID:015794638</ref><ref group="xtra">PMID:014596591</ref><ref group="xtra">PMID:015610006</ref><ref group="xtra">PMID:002905485</ref><ref group="xtra">PMID:002648161</ref><references group="xtra"/><references/>
	[[Category: Dodson, G G.]]		[[Category: Dodson, G G.]]
	[[Category: Hu, S Q.]]		[[Category: Hu, S Q.]]

OCA at 21:38, 20 October 2012

2012-10-20T21:38:09Z

←Older revision		Revision as of 21:38, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[3p2x]] is a 4 chain structure ~~of [[Molecular Playground/Insulin]]~~. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P2X OCA].	+	[[3p2x]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P2X OCA].

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

OCA at 13:49, 27 July 2012

2012-07-27T13:49:10Z

←Older revision		Revision as of 13:49, 27 July 2012
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-	[[Image:3p2x.~~jpg~~\|left\|200px]]	+	[[Image:3p2x.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_3p2x", 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_3p2x\| PDB=3p2x \| SCENE= }}		{{STRUCTURE_3p2x\| PDB=3p2x \| SCENE= }}

	===Insulin fibrillation is the Janus face of induced fit. A chiaral clamp stabilizes the native state at the expense of activity===		===Insulin fibrillation is the Janus face of induced fit. A chiaral clamp stabilizes the native state at the expense of activity===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_15794638}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 15794638 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_15794638}}		{{ABSTRACT_PUBMED_15794638}}

	==About this Structure==		==About this Structure==
-	[[3p2x]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P2X OCA].	+	[[3p2x]] is a 4 chain structure of [[Molecular Playground/Insulin]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P2X OCA].
		+
		+	==See Also==
		+	*[[Molecular Playground/Insulin\|Molecular Playground/Insulin]]

	==Reference==		==Reference==

OCA at 19:12, 23 November 2011

2011-11-23T19:12:56Z

←Older revision		Revision as of 19:12, 23 November 2011
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3p2x.jpg\|left\|200px]]

-	The ~~entry 3p2x~~ is ~~ON HOLD~~ ~~until Nov 18 2012~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3p2x", 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_3p2x\| PDB=3p2x \| SCENE= }}

-	~~Authors: Hua, Q.X., Wan, Z.L., Huang, K., Hu, S.Q., Phillip, N.F., Jia, W.H., Whittingham, J., Dodson, G.G., Katsoyannis, P.G., Weiss, M~~.A.	+	===Insulin fibrillation is the Janus face of induced fit. A chiaral clamp stabilizes the native state at the expense of activity===

-	~~Description~~: ~~Insulin fibrillation~~ is the ~~Janus face of induced fit~~. A ~~chiaral clamp stabilizes the native state at the expense of activity~~	+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_15794638}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 15794638 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_15794638}}
		+
		+	==About this Structure==
		+	[[3p2x]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P2X OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:015794638</ref><ref group="xtra">PMID:014596591</ref><ref group="xtra">PMID:015610006</ref><ref group="xtra">PMID:002905485</ref><ref group="xtra">PMID:002648161</ref><references group="xtra"/>
		+	[[Category: Dodson, G G.]]
		+	[[Category: Hu, S Q.]]
		+	[[Category: Hua, Q X.]]
		+	[[Category: Huang, K.]]
		+	[[Category: Jia, W H.]]
		+	[[Category: Katsoyannis, P G.]]
		+	[[Category: Phillip, N F.]]
		+	[[Category: Wan, Z L.]]
		+	[[Category: Weiss, M A.]]
		+	[[Category: Whittingham, J.]]
		+	[[Category: Global health]]
		+	[[Category: Hormone]]
		+	[[Category: Insulin fibrillation]]
		+	[[Category: Long-acting insulin analog]]
		+	[[Category: Receptor binding protein engineering]]
		+	[[Category: Zinc-binding site]]