7uha - Revision history

OCA at 11:21, 14 June 2023

2023-06-14T11:21:30Z

←Older revision		Revision as of 11:21, 14 June 2023
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	==NMR structure of the cNTnC-cTnI chimera bound to W6==		==NMR structure of the cNTnC-cTnI chimera bound to W6==
-	<StructureSection load='7uha' size='340' side='right'caption='[[7uha~~]], [[NMR_Ensembles_of_Models \| 10 NMR models~~]]' scene=''>	+	<StructureSection load='7uha' size='340' side='right'caption='[[7uha]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7uha]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UHA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UHA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7uha]] is a 1 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=7UHA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UHA FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=WW6:N-(5-aminopentyl)-5-chloronaphthalene-1-sulfonamide'>WW6</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=WW6:N-(5-aminopentyl)-5-chloronaphthalene-1-sulfonamide'>WW6</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;'>[[7uh9\|7uh9]]</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=7uha FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uha OCA], [https://pdbe.org/7uha PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uha RCSB], [https://www.ebi.ac.uk/pdbsum/7uha PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uha 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=7uha FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uha OCA], [https://pdbe.org/7uha PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uha RCSB], [https://www.ebi.ac.uk/pdbsum/7uha PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uha ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/TNNC1_HUMAN TNNC1_HUMAN]] Defects in TNNC1 are the cause of cardiomyopathy dilated type 1Z (CMD1Z) [MIM:[https://omim.org/entry/611879 611879]]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.<ref>PMID:15542288</ref> Defects in TNNC1 are the cause of familial hypertrophic cardiomyopathy type 13 (CMH13) [MIM:[https://omim.org/entry/613243 613243]]. A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.<ref>PMID:11385718</ref> <ref>PMID:16302972</ref> <ref>PMID:18572189</ref> <ref>PMID:19439414</ref>	+	[https://www.uniprot.org/uniprot/TNNC1_HUMAN TNNC1_HUMAN] Defects in TNNC1 are the cause of cardiomyopathy dilated type 1Z (CMD1Z) [MIM:[https://omim.org/entry/611879 611879]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.<ref>PMID:15542288</ref> Defects in TNNC1 are the cause of familial hypertrophic cardiomyopathy type 13 (CMH13) [MIM:[https://omim.org/entry/613243 613243]. A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.<ref>PMID:11385718</ref> <ref>PMID:16302972</ref> <ref>PMID:18572189</ref> <ref>PMID:19439414</ref> [https://www.uniprot.org/uniprot/TNNI3_HUMAN TNNI3_HUMAN] Defects in TNNI3 are the cause of familial hypertrophic cardiomyopathy type 7 (CMH7) [MIM:[https://omim.org/entry/613690 613690]. Familial hypertrophic cardiomyopathy is a hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.<ref>PMID:9241277</ref> <ref>PMID:11815426</ref> <ref>PMID:12707239</ref> <ref>PMID:12974739</ref> <ref>PMID:16199542</ref> Defects in TNNI3 are the cause of familial restrictive cardiomyopathy type 1 (RCM1) [MIM:[https://omim.org/entry/115210 115210]. RCM1 is a heart muscle disorder characterized by impaired filling of the ventricles with reduced diastolic volume, in the presence of normal or near normal wall thickness and systolic function.<ref>PMID:12531876</ref> Defects in TNNI3 are the cause of cardiomyopathy dilated type 2A (CMD2A) [MIM:[https://omim.org/entry/611880 611880]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.<ref>PMID:15070570</ref> Defects in TNNI3 are the cause of cardiomyopathy dilated type 1FF (CMD1FF) [MIM:[https://omim.org/entry/613286 613286]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/TNNC1_HUMAN TNNC1_HUMAN]] Troponin is the central regulatory protein of striated muscle contraction. Tn consists of three components: Tn-I which is the inhibitor of actomyosin ATPase, Tn-T which contains the binding site for tropomyosin and Tn-C. The binding of calcium to Tn-C abolishes the inhibitory action of Tn on actin filaments.	+	[https://www.uniprot.org/uniprot/TNNC1_HUMAN TNNC1_HUMAN] Troponin is the central regulatory protein of striated muscle contraction. Tn consists of three components: Tn-I which is the inhibitor of actomyosin ATPase, Tn-T which contains the binding site for tropomyosin and Tn-C. The binding of calcium to Tn-C abolishes the inhibitory action of Tn on actin filaments.[https://www.uniprot.org/uniprot/TNNI3_HUMAN TNNI3_HUMAN] Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity.
	<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: Cai, F]]	+	[[Category: Cai F]]
-	[[Category: Cockburn~~, K T~~]]	+	[[Category: Cockburn KT]]
-	[[Category: Kampourakis, T]]	+	[[Category: Kampourakis T]]
-	[[Category: Sykes~~, B D]]~~	+	[[Category: Sykes BD]]
-	~~[[Category: Calcium binding protein]]~~	+
-	~~[[Category: Calcium modulator]]~~	+
-	~~[[Category: Cardiac troponin]]~~	+
-	~~[[Category: Ef hand]]~~	+
-	~~[[Category: Metal binding protein~~]]	+

OCA at 07:35, 29 June 2022

2022-06-29T07:35:07Z

←Older revision		Revision as of 07:35, 29 June 2022
Line 1:		Line 1:

	==NMR structure of the cNTnC-cTnI chimera bound to W6==		==NMR structure of the cNTnC-cTnI chimera bound to W6==
-	<StructureSection load='7uha' size='340' side='right'caption='[[7uha]]' scene=''>	+	<StructureSection load='7uha' size='340' side='right'caption='[[7uha]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full ~~crystallographic~~ information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UHA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UHA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7uha]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UHA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UHA FirstGlance]. <br>
-	</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=7uha FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uha OCA], [https://pdbe.org/7uha PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uha RCSB], [https://www.ebi.ac.uk/pdbsum/7uha PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uha ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=WW6:N-(5-aminopentyl)-5-chloronaphthalene-1-sulfonamide'>WW6</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;'>[[7uh9\|7uh9]]</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=7uha FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uha OCA], [https://pdbe.org/7uha PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uha RCSB], [https://www.ebi.ac.uk/pdbsum/7uha PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uha ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[[https://www.uniprot.org/uniprot/TNNC1_HUMAN TNNC1_HUMAN]] Defects in TNNC1 are the cause of cardiomyopathy dilated type 1Z (CMD1Z) [MIM:[https://omim.org/entry/611879 611879]]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.<ref>PMID:15542288</ref> Defects in TNNC1 are the cause of familial hypertrophic cardiomyopathy type 13 (CMH13) [MIM:[https://omim.org/entry/613243 613243]]. A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.<ref>PMID:11385718</ref> <ref>PMID:16302972</ref> <ref>PMID:18572189</ref> <ref>PMID:19439414</ref>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/TNNC1_HUMAN TNNC1_HUMAN]] Troponin is the central regulatory protein of striated muscle contraction. Tn consists of three components: Tn-I which is the inhibitor of actomyosin ATPase, Tn-T which contains the binding site for tropomyosin and Tn-C. The binding of calcium to Tn-C abolishes the inhibitory action of Tn on actin filaments.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	W7 is a sarcomere inhibitor that decreases the calcium sensitivity of force development in cardiac muscle. W7 binds to the interface of the regulatory domain of cardiac troponin C (cNTnC) and the switch region of troponin I (cTnI), decreasing the binding of cTnI to cNTnC, presumably by electrostatic repulsion between the -NH3(+) group of W7 and basic amino acids in cTnI. W7 analogs with a -CO2(-) tail are inactive. To evaluate the importance of the location of the charged -NH3(+), we used a series of compounds W4, W6, W8, and W9, which have three less, one less, one more, and two more methylene groups in the tail region than W7. W6, W8, and W9 all bind tighter to cNTnC-cTnI chimera (cChimera) than W7, while W4 binds weaker. W4 and, strikingly, W6 have no effect on calcium sensitivity of force generation, while W8 and W9 decrease calcium sensitivity, but less than W7. The structures of the cChimera-W6 and cChimera-W8 complexes reveal that W6 and W8 bind to the same hydrophobic cleft as W7, with the aliphatic tail taking a similar route to the surface. NMR relaxation data show that internal flexibility in the tail of W7 is very limited. Alignment of the cChimera-W7 structure with the recent cryoEM structures of the cardiac sarcomere in the diastolic and systolic states reveals the critical location of the amino group. Small molecule induced structural changes can therefore affect the tightly balanced equilibrium between tethered components required for rapid contraction.
		+
		+	Drugging the Sarcomere, a Delicate Balance: Position of N-Terminal Charge of the Inhibitor W7.,Cai F, Kampourakis T, Cockburn KT, Sykes BD ACS Chem Biol. 2022 Jun 1. doi: 10.1021/acschembio.2c00126. PMID:35649123<ref>PMID:35649123</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7uha" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Cai F]]	+	[[Category: Cai, F]]
-	[[Category: Cockburn KT]]	+	[[Category: Cockburn, K T]]
-	[[Category: Kampourakis T]]	+	[[Category: Kampourakis, T]]
-	[[Category: Sykes BD]]	+	[[Category: Sykes, B D]]
		+	[[Category: Calcium binding protein]]
		+	[[Category: Calcium modulator]]
		+	[[Category: Cardiac troponin]]
		+	[[Category: Ef hand]]
		+	[[Category: Metal binding protein]]

OCA at 05:11, 15 June 2022

2022-06-15T05:11:29Z

←Older revision		Revision as of 05:11, 15 June 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7uha is ~~ON HOLD until Paper Publication~~	+	==NMR structure of the cNTnC-cTnI chimera bound to W6==
-		+	<StructureSection load='7uha' size='340' side='right'caption='[[7uha]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UHA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UHA FirstGlance]. <br>
-	~~Description~~:	+	</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=7uha FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uha OCA], [https://pdbe.org/7uha PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uha RCSB], [https://www.ebi.ac.uk/pdbsum/7uha PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uha ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Cai F]]
		+	[[Category: Cockburn KT]]
		+	[[Category: Kampourakis T]]
		+	[[Category: Sykes BD]]

OCA at 01:34, 21 April 2022

2022-04-21T01:34:26Z

←Older revision		Revision as of 01:34, 21 April 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7uha is ON HOLD	+	The entry 7uha is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7uha" [edit=sysop:move=sysop]

2022-04-06T09:04:04Z

Protected "7uha" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:04, 6 April 2022

OCA: New page: '''Unreleased structure''' The entry 7uha is ON HOLD Authors: Description: Category: Unreleased Structures

2022-04-06T09:04:02Z

New page: '''Unreleased structure''' The entry 7uha is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7uha is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]