1lxf - Revision history

OCA at 08:47, 22 May 2024

OCA — Wed, 22 May 2024 08:47:55 GMT

←Older revision		Revision as of 08:47, 22 May 2024
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=1lxf 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=1lxf ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Cardiac troponin C (cTnC) is the Ca(2+)-dependent switch for contraction in heart muscle and a potential target for drugs in the therapy of heart failure. Ca(2+) binding to the regulatory domain of cTnC (cNTnC) induces little structural change but sets the stage for cTnI binding. A large "closed" to "open" conformational transition occurs in the regulatory domain upon binding cTnI(147-163) or bepridil. This raises the question of whether cTnI(147-163) and bepridil compete for cNTnC.Ca(2+). In this work, we used two-dimensional (1)H,(15)N-heteronuclear single quantum coherence (HSQC) NMR spectroscopy to examine the binding of bepridil to cNTnC.Ca(2+) in the absence and presence of cTnI(147-163) and of cTnI(147-163) to cNTnC.Ca(2+) in the absence and presence of bepridil. The results show that bepridil and cTnI(147-163) bind cNTnC.Ca(2+) simultaneously but with negative cooperativity. The affinity of cTnI(147-163) for cNTnC.Ca(2+) is reduced approximately 3.5-fold by bepridil and vice versa. Using multinuclear and multidimensional NMR spectroscopy, we have determined the structure of the cNTnC.Ca(2+).cTnI(147-163).bepridil ternary complex. The structure reveals a binding site for cTnI(147-163) primarily located on the A/B interhelical interface and a binding site for bepridil in the hydrophobic pocket of cNTnC.Ca(2+). In the structure, the N terminus of the peptide clashes with part of the bepridil molecule, which explains the negative cooperativity between cTnI(147-163) and bepridil for cNTnC.Ca(2+). This structure provides insights into the features that are important for the design of cTnC-specific cardiotonic drugs, which may be used to modulate the Ca(2+) sensitivity of the myofilaments in heart muscle contraction.
		+
		+	Structure of the regulatory N-domain of human cardiac troponin C in complex with human cardiac troponin I147-163 and bepridil.,Wang X, Li MX, Sykes BD J Biol Chem. 2002 Aug 23;277(34):31124-33. Epub 2002 Jun 11. PMID:12060657<ref>PMID:12060657</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 1lxf" style="background-color:#fffaf0;"></div>

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

OCA at 08:28, 10 April 2024

OCA — Wed, 10 Apr 2024 08:28:57 GMT

←Older revision		Revision as of 08:28, 10 April 2024
Line 1:		Line 1:

	==Structure of the Regulatory N-domain of Human Cardiac Troponin C in Complex with Human Cardiac Troponin-I(147-163) and Bepridil==		==Structure of the Regulatory N-domain of Human Cardiac Troponin C in Complex with Human Cardiac Troponin-I(147-163) and Bepridil==
-	<StructureSection load='1lxf' size='340' side='right'caption='[[1lxf~~]], [[NMR_Ensembles_of_Models \| 30 NMR models~~]]' scene=''>	+	<StructureSection load='1lxf' size='340' side='right'caption='[[1lxf]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1lxf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LXF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LXF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1lxf]] 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=1LXF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LXF FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BEP:1-ISOBUTOXY-2-PYRROLIDINO-3[N-BENZYLANILINO]+PROPANE'>BEP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TNNC ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BEP:1-ISOBUTOXY-2-PYRROLIDINO-3[N-BENZYLANILINO]+PROPANE'>BEP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=1lxf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lxf OCA], [https://pdbe.org/1lxf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lxf RCSB], [https://www.ebi.ac.uk/pdbsum/1lxf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lxf 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=1lxf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lxf OCA], [https://pdbe.org/1lxf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lxf RCSB], [https://www.ebi.ac.uk/pdbsum/1lxf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lxf 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/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.	+	[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 ==		== 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/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.	+	[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.
	== 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=1lxf 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=1lxf ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Cardiac troponin C (cTnC) is the Ca(2+)-dependent switch for contraction in heart muscle and a potential target for drugs in the therapy of heart failure. Ca(2+) binding to the regulatory domain of cTnC (cNTnC) induces little structural change but sets the stage for cTnI binding. A large "closed" to "open" conformational transition occurs in the regulatory domain upon binding cTnI(147-163) or bepridil. This raises the question of whether cTnI(147-163) and bepridil compete for cNTnC.Ca(2+). In this work, we used two-dimensional (1)H,(15)N-heteronuclear single quantum coherence (HSQC) NMR spectroscopy to examine the binding of bepridil to cNTnC.Ca(2+) in the absence and presence of cTnI(147-163) and of cTnI(147-163) to cNTnC.Ca(2+) in the absence and presence of bepridil. The results show that bepridil and cTnI(147-163) bind cNTnC.Ca(2+) simultaneously but with negative cooperativity. The affinity of cTnI(147-163) for cNTnC.Ca(2+) is reduced approximately 3.5-fold by bepridil and vice versa. Using multinuclear and multidimensional NMR spectroscopy, we have determined the structure of the cNTnC.Ca(2+).cTnI(147-163).bepridil ternary complex. The structure reveals a binding site for cTnI(147-163) primarily located on the A/B interhelical interface and a binding site for bepridil in the hydrophobic pocket of cNTnC.Ca(2+). In the structure, the N terminus of the peptide clashes with part of the bepridil molecule, which explains the negative cooperativity between cTnI(147-163) and bepridil for cNTnC.Ca(2+). This structure provides insights into the features that are important for the design of cTnC-specific cardiotonic drugs, which may be used to modulate the Ca(2+) sensitivity of the myofilaments in heart muscle contraction.
-
-	Structure of the regulatory N-domain of human cardiac troponin C in complex with human cardiac troponin I147-163 and bepridil.,Wang X, Li MX, Sykes BD J Biol Chem. 2002 Aug 23;277(34):31124-33. Epub 2002 Jun 11. PMID:12060657<ref>PMID:12060657</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 1lxf" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
-	*[[Troponin\|Troponin]]	+	*[[Troponin 3D structures\|Troponin 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Li~~, M X~~]]	+	[[Category: Li MX]]
-	[[Category: Sykes~~, B D~~]]	+	[[Category: Sykes BD]]
-	[[Category: Wang, X]]	+	[[Category: Wang X]]
-	~~[[Category: Bepridil]]~~	+
-	~~[[Category: Cardiac troponin c-drug interaction]]~~	+
-	~~[[Category: Cardiac troponin i-drug interaction]]~~	+
-	~~[[Category: Metal binding protein]]~~	+
-	~~[[Category: Muscle]]~~	+
-	~~[[Category: Protein binding~~]]	+

OCA at 08:15, 23 February 2022

OCA — Wed, 23 Feb 2022 08:15:26 GMT

OCA at 08:31, 2 December 2020

OCA — Wed, 02 Dec 2020 08:31:22 GMT

←Older revision		Revision as of 08:31, 2 December 2020
Line 1:		Line 1:

	==Structure of the Regulatory N-domain of Human Cardiac Troponin C in Complex with Human Cardiac Troponin-I(147-163) and Bepridil==		==Structure of the Regulatory N-domain of Human Cardiac Troponin C in Complex with Human Cardiac Troponin-I(147-163) and Bepridil==
-	<StructureSection load='1lxf' size='340' side='right' caption='[[1lxf]], [[NMR_Ensembles_of_Models \| 30 NMR models]]' scene=''>	+	<StructureSection load='1lxf' size='340' side='right'caption='[[1lxf]], [[NMR_Ensembles_of_Models \| 30 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1lxf]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LXF OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1LXF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1lxf]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LXF OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1LXF FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BEP:1-ISOBUTOXY-2-PYRROLIDINO-3[N-BENZYLANILINO]+PROPANE'>BEP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BEP:1-ISOBUTOXY-2-PYRROLIDINO-3[N-BENZYLANILINO]+PROPANE'>BEP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TNNC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TNNC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=1lxf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lxf OCA], [http://pdbe.org/1lxf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1lxf RCSB], [http://www.ebi.ac.uk/pdbsum/1lxf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1lxf ProSAT]</span></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=1lxf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lxf OCA], [http://pdbe.org/1lxf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1lxf RCSB], [http://www.ebi.ac.uk/pdbsum/1lxf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1lxf ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 16:		Line 16:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lx/1lxf_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lx/1lxf_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 31:		Line 31:
	</div>		</div>
	<div class="pdbe-citations 1lxf" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1lxf" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Troponin\|Troponin]]
	== References ==		== References ==
	<references/>		<references/>
Line 36:		Line 39:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Li, M X]]		[[Category: Li, M X]]
	[[Category: Sykes, B D]]		[[Category: Sykes, B D]]

OCA at 10:35, 18 October 2017

OCA — Wed, 18 Oct 2017 10:35:08 GMT

←Older revision		Revision as of 10:35, 18 October 2017
Line 1:		Line 1:
		+
	==Structure of the Regulatory N-domain of Human Cardiac Troponin C in Complex with Human Cardiac Troponin-I(147-163) and Bepridil==		==Structure of the Regulatory N-domain of Human Cardiac Troponin C in Complex with Human Cardiac Troponin-I(147-163) and Bepridil==
	<StructureSection load='1lxf' size='340' side='right' caption='[[1lxf]], [[NMR_Ensembles_of_Models \| 30 NMR models]]' scene=''>		<StructureSection load='1lxf' size='340' side='right' caption='[[1lxf]], [[NMR_Ensembles_of_Models \| 30 NMR models]]' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BEP:1-ISOBUTOXY-2-PYRROLIDINO-3[N-BENZYLANILINO]+PROPANE'>BEP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BEP:1-ISOBUTOXY-2-PYRROLIDINO-3[N-BENZYLANILINO]+PROPANE'>BEP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TNNC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TNNC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=1lxf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lxf OCA], [http://pdbe.org/1lxf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1lxf RCSB], [http://www.ebi.ac.uk/pdbsum/1lxf 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=1lxf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lxf OCA], [http://pdbe.org/1lxf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1lxf RCSB], [http://www.ebi.ac.uk/pdbsum/1lxf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1lxf ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 19:		Line 20:
	<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=1lxf ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 30:		Line 31:
	</div>		</div>
	<div class="pdbe-citations 1lxf" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1lxf" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Troponin\|Troponin]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 15:01, 11 September 2015

OCA — Fri, 11 Sep 2015 15:01:06 GMT

←Older revision		Revision as of 15:01, 11 September 2015
Line 2:		Line 2:
	<StructureSection load='1lxf' size='340' side='right' caption='[[1lxf]], [[NMR_Ensembles_of_Models \| 30 NMR models]]' scene=''>		<StructureSection load='1lxf' size='340' side='right' caption='[[1lxf]], [[NMR_Ensembles_of_Models \| 30 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1lxf]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LXF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1LXF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1lxf]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LXF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1LXF FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BEP:1-ISOBUTOXY-2-PYRROLIDINO-3[N-BENZYLANILINO]+PROPANE'>BEP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BEP:1-ISOBUTOXY-2-PYRROLIDINO-3[N-BENZYLANILINO]+PROPANE'>BEP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TNNC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TNNC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=1lxf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lxf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1lxf RCSB], [http://www.ebi.ac.uk/pdbsum/1lxf 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=1lxf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lxf OCA], [http://pdbe.org/1lxf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1lxf RCSB], [http://www.ebi.ac.uk/pdbsum/1lxf 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 1lxf" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 36:		Line 37:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Li, M X]]		[[Category: Li, M X]]
	[[Category: Sykes, B D]]		[[Category: Sykes, B D]]

OCA at 15:19, 5 January 2015

OCA — Mon, 05 Jan 2015 15:19:23 GMT

←Older revision		Revision as of 15:19, 5 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1lxf]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LXF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1LXF FirstGlance]. <br>		<table><tr><td colspan='2'>[[1lxf]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LXF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1LXF FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BEP:1-ISOBUTOXY-2-PYRROLIDINO-3[N-BENZYLANILINO]+PROPANE'>BEP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BEP:1-ISOBUTOXY-2-PYRROLIDINO-3[N-BENZYLANILINO]+PROPANE'>BEP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TNNC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TNNC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=1lxf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lxf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1lxf RCSB], [http://www.ebi.ac.uk/pdbsum/1lxf 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=1lxf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lxf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1lxf RCSB], [http://www.ebi.ac.uk/pdbsum/1lxf PDBsum]</span></td></tr>
-	<table>	+	</table>
	== Disease ==		== Disease ==
	[[http://www.uniprot.org/uniprot/TNNC1_HUMAN TNNC1_HUMAN]] Defects in TNNC1 are the cause of cardiomyopathy dilated type 1Z (CMD1Z) [MIM:[http://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:[http://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> [[http://www.uniprot.org/uniprot/TNNI3_HUMAN TNNI3_HUMAN]] Defects in TNNI3 are the cause of familial hypertrophic cardiomyopathy type 7 (CMH7) [MIM:[http://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:[http://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:[http://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:[http://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.		[[http://www.uniprot.org/uniprot/TNNC1_HUMAN TNNC1_HUMAN]] Defects in TNNC1 are the cause of cardiomyopathy dilated type 1Z (CMD1Z) [MIM:[http://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:[http://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> [[http://www.uniprot.org/uniprot/TNNI3_HUMAN TNNI3_HUMAN]] Defects in TNNI3 are the cause of familial hypertrophic cardiomyopathy type 7 (CMH7) [MIM:[http://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:[http://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:[http://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:[http://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.
Line 37:		Line 37:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Li, M X.]]	+	[[Category: Li, M X]]
-	[[Category: Sykes, B D.]]	+	[[Category: Sykes, B D]]
-	[[Category: Wang, X.]]	+	[[Category: Wang, X]]
	[[Category: Bepridil]]		[[Category: Bepridil]]
	[[Category: Cardiac troponin c-drug interaction]]		[[Category: Cardiac troponin c-drug interaction]]

OCA at 16:47, 29 September 2014

OCA — Mon, 29 Sep 2014 16:47:56 GMT

←Older revision		Revision as of 16:47, 29 September 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_1lxf\| PDB=1lxf \| SCENE= }}~~	+	==Structure of the Regulatory N-domain of Human Cardiac Troponin C in Complex with Human Cardiac Troponin-I(147-163) and Bepridil==
-	===Structure of the Regulatory N-domain of Human Cardiac Troponin C in Complex with Human Cardiac Troponin-I(147-163) and Bepridil===	+	<StructureSection load='1lxf' size='340' side='right' caption='[[1lxf]], [[NMR_Ensembles_of_Models \| 30 NMR models]]' scene=''>
-	~~{{ABSTRACT_PUBMED_12060657}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1lxf]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LXF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1LXF FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BEP:1-ISOBUTOXY-2-PYRROLIDINO-3[N-BENZYLANILINO]+PROPANE'>BEP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TNNC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=1lxf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lxf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1lxf RCSB], [http://www.ebi.ac.uk/pdbsum/1lxf PDBsum]</span></td></tr>
		+	<table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/TNNC1_HUMAN TNNC1_HUMAN]] Defects in TNNC1 are the cause of cardiomyopathy dilated type 1Z (CMD1Z) [MIM:[http://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:[http://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> [[http://www.uniprot.org/uniprot/TNNI3_HUMAN TNNI3_HUMAN]] Defects in TNNI3 are the cause of familial hypertrophic cardiomyopathy type 7 (CMH7) [MIM:[http://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:[http://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:[http://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:[http://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 ==
		+	[[http://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. [[http://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.
		+	== 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/lx/1lxf_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 ==
		+	Cardiac troponin C (cTnC) is the Ca(2+)-dependent switch for contraction in heart muscle and a potential target for drugs in the therapy of heart failure. Ca(2+) binding to the regulatory domain of cTnC (cNTnC) induces little structural change but sets the stage for cTnI binding. A large "closed" to "open" conformational transition occurs in the regulatory domain upon binding cTnI(147-163) or bepridil. This raises the question of whether cTnI(147-163) and bepridil compete for cNTnC.Ca(2+). In this work, we used two-dimensional (1)H,(15)N-heteronuclear single quantum coherence (HSQC) NMR spectroscopy to examine the binding of bepridil to cNTnC.Ca(2+) in the absence and presence of cTnI(147-163) and of cTnI(147-163) to cNTnC.Ca(2+) in the absence and presence of bepridil. The results show that bepridil and cTnI(147-163) bind cNTnC.Ca(2+) simultaneously but with negative cooperativity. The affinity of cTnI(147-163) for cNTnC.Ca(2+) is reduced approximately 3.5-fold by bepridil and vice versa. Using multinuclear and multidimensional NMR spectroscopy, we have determined the structure of the cNTnC.Ca(2+).cTnI(147-163).bepridil ternary complex. The structure reveals a binding site for cTnI(147-163) primarily located on the A/B interhelical interface and a binding site for bepridil in the hydrophobic pocket of cNTnC.Ca(2+). In the structure, the N terminus of the peptide clashes with part of the bepridil molecule, which explains the negative cooperativity between cTnI(147-163) and bepridil for cNTnC.Ca(2+). This structure provides insights into the features that are important for the design of cTnC-specific cardiotonic drugs, which may be used to modulate the Ca(2+) sensitivity of the myofilaments in heart muscle contraction.

-	~~==Disease==~~	+	Structure of the regulatory N-domain of human cardiac troponin C in complex with human cardiac troponin I147-163 and bepridil.,Wang X, Li MX, Sykes BD J Biol Chem. 2002 Aug 23;277(34):31124-33. Epub 2002 Jun 11. PMID:12060657<ref>PMID:12060657</ref>
-	~~[[http://www.uniprot.org/uniprot/TNNC1_HUMAN TNNC1_HUMAN]] Defects in TNNC1 are the cause~~ of cardiomyopathy dilated type 1Z (CMD1Z) [MIM:[http://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:[http://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> [[http://www.uniprot.org/uniprot/TNNI3_HUMAN TNNI3_HUMAN]] Defects in TNNI3 are the cause of familial hypertrophic cardiomyopathy type 7 (CMH7) [MIM:[http://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~~:~~[http://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:[http://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:[http://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==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[http:~~//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~~. ~~[[http://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>
-		+
-	~~==About this Structure==~~	+
-	~~[[1lxf]] is a 2 chain structure with sequence from [http:~~/~~/en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LXF OCA].~~	+

	==See Also==		==See Also==
	*[[Troponin\|Troponin]]		*[[Troponin\|Troponin]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:012060657</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Li, M X.]]		[[Category: Li, M X.]]

OCA at 20:30, 24 March 2013

OCA — Sun, 24 Mar 2013 20:30:35 GMT

←Older revision		Revision as of 20:30, 24 March 2013
Line 1:		Line 1:
-	[[Image:1lxf.png\|left\|200px]]
-
	{{STRUCTURE_1lxf\| PDB=1lxf \| SCENE= }}		{{STRUCTURE_1lxf\| PDB=1lxf \| SCENE= }}
-
	===Structure of the Regulatory N-domain of Human Cardiac Troponin C in Complex with Human Cardiac Troponin-I(147-163) and Bepridil===		===Structure of the Regulatory N-domain of Human Cardiac Troponin C in Complex with Human Cardiac Troponin-I(147-163) and Bepridil===
		+	{{ABSTRACT_PUBMED_12060657}}

-	~~{{ABSTRACT_PUBMED_12060657}}~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/TNNC1_HUMAN TNNC1_HUMAN]] Defects in TNNC1 are the cause of cardiomyopathy dilated type 1Z (CMD1Z) [MIM:[http://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:[http://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> [[http://www.uniprot.org/uniprot/TNNI3_HUMAN TNNI3_HUMAN]] Defects in TNNI3 are the cause of familial hypertrophic cardiomyopathy type 7 (CMH7) [MIM:[http://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:[http://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:[http://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:[http://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==
		+	[[http://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. [[http://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.

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

	==Reference==		==Reference==
-	<ref group="xtra">PMID:012060657</ref><references group="xtra"/>	+	<ref group="xtra">PMID:012060657</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Li, M X.]]		[[Category: Li, M X.]]

OCA at 19:46, 20 October 2012

OCA — Sat, 20 Oct 2012 19:46:29 GMT

←Older revision		Revision as of 19:46, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[1lxf]] is a 2 chain structure ~~of [[Troponin]]~~ with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LXF OCA].	+	[[1lxf]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LXF OCA].

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

←Older revision		Revision as of 08:15, 23 February 2022
Line 3:		Line 3:
	<StructureSection load='1lxf' size='340' side='right'caption='[[1lxf]], [[NMR_Ensembles_of_Models \| 30 NMR models]]' scene=''>		<StructureSection load='1lxf' size='340' side='right'caption='[[1lxf]], [[NMR_Ensembles_of_Models \| 30 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1lxf]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LXF OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=1LXF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1lxf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LXF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LXF FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BEP:1-ISOBUTOXY-2-PYRROLIDINO-3[N-BENZYLANILINO]+PROPANE'>BEP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BEP:1-ISOBUTOXY-2-PYRROLIDINO-3[N-BENZYLANILINO]+PROPANE'>BEP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TNNC ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TNNC ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=1lxf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lxf OCA], [~~http~~://pdbe.org/1lxf PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1lxf RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1lxf PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1lxf 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=1lxf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lxf OCA], [https://pdbe.org/1lxf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lxf RCSB], [https://www.ebi.ac.uk/pdbsum/1lxf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lxf ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/TNNC1_HUMAN TNNC1_HUMAN]] Defects in TNNC1 are the cause of cardiomyopathy dilated type 1Z (CMD1Z) [MIM:[~~http~~://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:[~~http~~://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> [[~~http~~://www.uniprot.org/uniprot/TNNI3_HUMAN TNNI3_HUMAN]] Defects in TNNI3 are the cause of familial hypertrophic cardiomyopathy type 7 (CMH7) [MIM:[~~http~~://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:[~~http~~://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:[~~http~~://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:[~~http~~://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.	+	[[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 ==
-	[[~~http~~://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. [[~~http~~://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.	+	[[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.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]