1lxf

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{{Seed}}
 
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[[Image:1lxf.png|left|200px]]
 
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==Structure of the Regulatory N-domain of Human Cardiac Troponin C in Complex with Human Cardiac Troponin-I(147-163) and Bepridil==
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The line below this paragraph, containing "STRUCTURE_1lxf", creates the "Structure Box" on the page.
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<StructureSection load='1lxf' size='340' side='right'caption='[[1lxf]]' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<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>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<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>
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{{STRUCTURE_1lxf| PDB=1lxf | SCENE= }}
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<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>
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</table>
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== Disease ==
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[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>
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== Function ==
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[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.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lx/1lxf_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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===Structure of the Regulatory N-domain of Human Cardiac Troponin C in Complex with Human Cardiac Troponin-I(147-163) and Bepridil===
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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>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 1lxf" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_12060657}}, adds the Publication Abstract to the page
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*[[Troponin 3D structures|Troponin 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 12060657 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_12060657}}
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__TOC__
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</StructureSection>
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==About this Structure==
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1LXF is a 2 chains structure of sequences 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].
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==Reference==
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<ref group="xtra">PMID:12060657</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Li, M X.]]
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[[Category: Large Structures]]
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[[Category: Sykes, B D.]]
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[[Category: Li MX]]
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[[Category: Wang, X.]]
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[[Category: Sykes BD]]
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[[Category: Bepridil]]
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[[Category: Wang X]]
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[[Category: Cardiac troponin c-drug interaction]]
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[[Category: Cardiac troponin i-drug interaction]]
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[[Category: Muscle]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 18 01:00:51 2009''
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Current revision

Structure of the Regulatory N-domain of Human Cardiac Troponin C in Complex with Human Cardiac Troponin-I(147-163) and Bepridil

PDB ID 1lxf

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