3rv5

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[[Image:3rv5.png|left|200px]]
 
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==Crystal structure of human cardiac troponin C regulatory domain in complex with cadmium and deoxycholic acid==
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The line below this paragraph, containing "STRUCTURE_3rv5", creates the "Structure Box" on the page.
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<StructureSection load='3rv5' size='340' side='right'caption='[[3rv5]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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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'>[[3rv5]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RV5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RV5 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=DXC:(3ALPHA,5BETA,12ALPHA)-3,12-DIHYDROXYCHOLAN-24-OIC+ACID'>DXC</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
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{{STRUCTURE_3rv5| PDB=3rv5 | 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=3rv5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rv5 OCA], [https://pdbe.org/3rv5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rv5 RCSB], [https://www.ebi.ac.uk/pdbsum/3rv5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rv5 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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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The amino-terminal regulatory domain of cardiac troponin C (cNTnC) plays an important role as the calcium sensor for the troponin complex. Calcium binding to cNTnC results in conformational changes that trigger a cascade of events that lead to cardiac muscle contraction. The cardiac N-terminal domain of TnC consists of two EF-hand calcium binding motifs, one of which is dysfunctional in binding calcium. Nevertheless, the defunct EF-hand still maintains a role in cNTnC function. For its structural analysis by X-ray crystallography, human cNTnC with the wild-type primary sequence was crystallized under a novel crystallization condition. The crystal structure was solved by the single-wavelength anomalous dispersion method and refined to 2.2 A resolution. The structure displays several novel features. Firstly, both EF-hand motifs coordinate cadmium ions derived from the crystallization milieu. Secondly, the ion coordination in the defunct EF-hand motif accompanies unusual changes in the protein conformation. Thirdly, deoxycholic acid, also derived from the crystallization milieu, is bound in the central hydrophobic cavity. This is reminiscent of the interactions observed for cardiac calcium sensitizer drugs that bind to the same core region and maintain the "open" conformational state of calcium-bound cNTnC. The cadmium ion coordination in the defunct EF-hand indicates that this vestigial calcium binding site retains the structural and functional elements that allow it to coordinate a cadmium ion. However, it is a result of, or concomitant with, large and unusual structural changes in cNTnC.
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===Crystal structure of human cardiac troponin C regulatory domain in complex with cadmium and deoxycholic acid===
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Crystal structure of cardiac troponin C regulatory domain in complex with cadmium and deoxycholic Acid reveals novel conformation.,Li AY, Lee J, Borek D, Otwinowski Z, Tibbits GF, Paetzel M J Mol Biol. 2011 Oct 28;413(3):699-711. Epub 2011 Sep 6. PMID:21920370<ref>PMID:21920370</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 3rv5" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_21920370}}, 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 21920370 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_21920370}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[3rv5]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RV5 OCA].
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==Reference==
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<ref group="xtra">PMID:021920370</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Borek, D.]]
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[[Category: Large Structures]]
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[[Category: Lee, J.]]
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[[Category: Borek D]]
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[[Category: Li, A Y.]]
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[[Category: Lee J]]
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[[Category: Otwinowski, Z.]]
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[[Category: Li AY]]
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[[Category: Paetzel, M.]]
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[[Category: Otwinowski Z]]
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[[Category: Tibbits, G.]]
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[[Category: Paetzel M]]
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[[Category: Calcium sensor]]
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[[Category: Tibbits G]]
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[[Category: Contractile protein]]
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[[Category: Helix-loop-helix ef-hand motif]]
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[[Category: Metal ion coordination]]
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Current revision

Crystal structure of human cardiac troponin C regulatory domain in complex with cadmium and deoxycholic acid

PDB ID 3rv5

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