5wdm - Revision history

OCA at 14:11, 4 October 2023

2023-10-04T14:11:17Z

←Older revision		Revision as of 14:11, 4 October 2023
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	<StructureSection load='5wdm' size='340' side='right'caption='[[5wdm]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='5wdm' size='340' side='right'caption='[[5wdm]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5wdm]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WDM OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5WDM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5wdm]] is a 6 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=5WDM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WDM FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5wdm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wdm OCA], [~~http~~://pdbe.org/5wdm PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5wdm RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5wdm PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5wdm ProSAT]</span></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]] 2.803Å</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=5wdm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wdm OCA], [https://pdbe.org/5wdm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wdm RCSB], [https://www.ebi.ac.uk/pdbsum/5wdm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wdm ProSAT]</span></td></tr>
	</table>		</table>
		+	== 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>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/~~A6XGL2_HUMAN A6XGL2_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 ~~(By similarity)~~.~~[SAAS:SAAS022353_004_028339]~~	+	[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 ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Aldabbagh, K]]	+	[[Category: Aldabbagh K]]
-	[[Category: Peng, Y]]	+	[[Category: Peng Y]]
-	[[Category: Yee~~, V C]]~~	+	[[Category: Yee VC]]
-	~~[[Category: Designed insulin]]~~	+
-	~~[[Category: Hexamer]]~~	+
-	~~[[Category: Hormone]]~~	+
-	~~[[Category: Single chain~~]]	+

OCA at 08:51, 30 September 2020

2020-09-30T08:51:41Z

←Older revision		Revision as of 08:51, 30 September 2020
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	==An ultra-stable single-chain insulin analog resists thermal inactivation and exhibits biological signaling duration equivalent to the native protein==		==An ultra-stable single-chain insulin analog resists thermal inactivation and exhibits biological signaling duration equivalent to the native protein==
-	<StructureSection load='5wdm' size='340' side='right' caption='[[5wdm]], [[Resolution\|resolution]] 2.80Å' scene=''>	+	<StructureSection load='5wdm' size='340' side='right'caption='[[5wdm]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5wdm]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WDM OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5WDM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5wdm]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WDM OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5WDM FirstGlance]. <br>
-	</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=5wdm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wdm OCA], [http://pdbe.org/5wdm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wdm RCSB], [http://www.ebi.ac.uk/pdbsum/5wdm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wdm ProSAT]</span></td></tr>	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5wdm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wdm OCA], [http://pdbe.org/5wdm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wdm RCSB], [http://www.ebi.ac.uk/pdbsum/5wdm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wdm ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Aldabbagh, K]]		[[Category: Aldabbagh, K]]
	[[Category: Peng, Y]]		[[Category: Peng, Y]]

OCA at 10:32, 22 November 2017

2017-11-22T10:32:45Z

←Older revision		Revision as of 10:32, 22 November 2017
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	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/A6XGL2_HUMAN A6XGL2_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 (By similarity).[SAAS:SAAS022353_004_028339]		[[http://www.uniprot.org/uniprot/A6XGL2_HUMAN A6XGL2_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 (By similarity).[SAAS:SAAS022353_004_028339]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Thermal degradation of insulin complicates its delivery and use. Previous efforts to engineer ultra-stable analogs were confounded by prolonged cellular signaling in vivo, complicating mealtime therapy and of unclear safety. We therefore sought an ultra-stable analog whose potency and duration of action on intravenous bolus injection in diabetic rats are indistinguishable from wild-type (WT) insulin. Here, we describe the structure, function and stability of such an analog: a 57-residue single-chain insulin (SCI) with multiple acidic substitutions. Cell-based studies revealed native-like signaling properties with negligible mitogenic activity. Its crystal structure, determined as a novel zinc-free hexamer at 2.8 A, revealed a native insulin fold with incomplete or absent electron density in the C domain; complementary NMR studies are described in a companion article. The stability of the analog (DeltaGu 5.0(+/-0.1) kcal/mol at 25 degrees C) was greater than that of WT insulin (3.3(+/-0.1) kcal/mol). On gentle agitation the SCI retained full activity for >140 days at 45 degrees C and >48 hours at 75 degrees C. Whereas WT insulin forms large and heterogeneous aggregates above the standard 0.6 mM pharmaceutical strength, perturbing the pharmacokinetic properties of concentrated formulations, dynamic light scattering and size-exclusion chromatography revealed only limited SCI self-assembly and aggregation in the concentration range 1-7 mM. These findings indicate that marked resistance to thermal inactivation in vitro is compatible with native duration of activity in vivo. Such a combination of favorable biophysical and biological properties suggests that SCIs could provide a global therapeutic platform without a cold chain.
		+
		+	An ultra-stable single-chain insulin analog resists thermal inactivation and exhibits biological signaling duration equivalent to the native protein.,Glidden MD, Aldabbagh K, Phillips NB, Carr K, Chen YS, Whittaker J, Phillips M, Wickramasinghe NP, Rege N, Swain M, Peng Y, Yang Y, Lawrence MC, Yee VC, Ismail-Beigi F, Weiss MA J Biol Chem. 2017 Nov 7. pii: jbc.M117.808626. doi: 10.1074/jbc.M117.808626. PMID:29114035<ref>PMID:29114035</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5wdm" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 07:35, 15 November 2017

2017-11-15T07:35:01Z

←Older revision		Revision as of 07:35, 15 November 2017
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-	'''Unreleased structure'''

-	~~The entry~~ 5wdm is ~~ON HOLD until Paper Publication~~	+	==An ultra-stable single-chain insulin analog resists thermal inactivation and exhibits biological signaling duration equivalent to the native protein==
-		+	<StructureSection load='5wdm' size='340' side='right' caption='[[5wdm]], [[Resolution\|resolution]] 2.80Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5wdm]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WDM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WDM FirstGlance]. <br>
-	~~Description~~:	+	</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=5wdm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wdm OCA], [http://pdbe.org/5wdm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wdm RCSB], [http://www.ebi.ac.uk/pdbsum/5wdm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wdm ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/A6XGL2_HUMAN A6XGL2_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 (By similarity).[SAAS:SAAS022353_004_028339]
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Aldabbagh, K]]
		+	[[Category: Peng, Y]]
		+	[[Category: Yee, V C]]
		+	[[Category: Designed insulin]]
		+	[[Category: Hexamer]]
		+	[[Category: Hormone]]
		+	[[Category: Single chain]]

OCA: Protected "5wdm" [edit=sysop:move=sysop]

2017-09-27T14:43:03Z

Protected "5wdm" [edit=sysop:move=sysop]

←Older revision

Revision as of 14:43, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 5wdm is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

2017-09-27T14:43:02Z

New page: '''Unreleased structure''' The entry 5wdm is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5wdm is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]