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[[Image:1dtl.gif|left|200px]]
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{{STRUCTURE_1dtl|  PDB=1dtl  |  SCENE=  }}
'''CRYSTAL STRUCTURE OF CALCIUM-SATURATED (3CA2+) CARDIAC TROPONIN C COMPLEXED WITH THE CALCIUM SENSITIZER BEPRIDIL AT 2.15 A RESOLUTION'''


==CRYSTAL STRUCTURE OF CALCIUM-SATURATED (3CA2+) CARDIAC TROPONIN C COMPLEXED WITH THE CALCIUM SENSITIZER BEPRIDIL AT 2.15 A RESOLUTION==
<StructureSection load='1dtl' size='340' side='right'caption='[[1dtl]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1dtl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DTL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1DTL FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.15&#8491;</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=1dtl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dtl OCA], [https://pdbe.org/1dtl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1dtl RCSB], [https://www.ebi.ac.uk/pdbsum/1dtl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1dtl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TNNC1_CHICK TNNC1_CHICK] 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 ==
[[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/dt/1dtl_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/main_output.php?pdb_ID=1dtl ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cardiac troponin C (cTnC) is the calcium-dependent switch for contraction in heart muscle and a potential target for drugs in the therapy of congestive heart failure. This calmodulin-like protein consists of two lobes connected by a central linker; each lobe contains two EF-hand domains. The regulatory N-terminal lobe of cTnC, unlike that of skeletal troponin C (sTnC), contains only one functional EF-hand and does not open fully upon the binding of Ca(2+). We have determined the crystal structure of cTnC, with three bound Ca(2+) ions, complexed with the calcium-sensitizer bepridil, to 2.15-A resolution. In contrast to apo- and 3Ca(2+)-cTnC, the drug-bound complex displays a fully open N-terminal lobe similar to the N-terminal lobes of 4Ca(2+)-sTnC and cTnC bound to a C-terminal fragment of cardiac troponin I (residues 147-163). The closing of the lobe is sterically hindered by one of the three bound bepridils. Our results provide a structural basis for the Ca(2+)-sensitizing effect of bepridil and reveal the details of a distinctive two-stage mechanism for Ca(2+) regulation by troponin C in cardiac muscle.


==Overview==
Bepridil opens the regulatory N-terminal lobe of cardiac troponin C.,Li Y, Love ML, Putkey JA, Cohen C Proc Natl Acad Sci U S A. 2000 May 9;97(10):5140-5. PMID:10792039<ref>PMID:10792039</ref>
Cardiac troponin C (cTnC) is the calcium-dependent switch for contraction in heart muscle and a potential target for drugs in the therapy of congestive heart failure. This calmodulin-like protein consists of two lobes connected by a central linker; each lobe contains two EF-hand domains. The regulatory N-terminal lobe of cTnC, unlike that of skeletal troponin C (sTnC), contains only one functional EF-hand and does not open fully upon the binding of Ca(2+). We have determined the crystal structure of cTnC, with three bound Ca(2+) ions, complexed with the calcium-sensitizer bepridil, to 2.15-A resolution. In contrast to apo- and 3Ca(2+)-cTnC, the drug-bound complex displays a fully open N-terminal lobe similar to the N-terminal lobes of 4Ca(2+)-sTnC and cTnC bound to a C-terminal fragment of cardiac troponin I (residues 147-163). The closing of the lobe is sterically hindered by one of the three bound bepridils. Our results provide a structural basis for the Ca(2+)-sensitizing effect of bepridil and reveal the details of a distinctive two-stage mechanism for Ca(2+) regulation by troponin C in cardiac muscle.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1DTL is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DTL OCA].
</div>
<div class="pdbe-citations 1dtl" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Bepridil opens the regulatory N-terminal lobe of cardiac troponin C., Li Y, Love ML, Putkey JA, Cohen C, Proc Natl Acad Sci U S A. 2000 May 9;97(10):5140-5. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10792039 10792039]
*[[Troponin 3D structures|Troponin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Gallus gallus]]
[[Category: Gallus gallus]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Cohen, C.]]
[[Category: Cohen C]]
[[Category: Li, Y.]]
[[Category: Li Y]]
[[Category: Love, M L.]]
[[Category: Love ML]]
[[Category: Putkey, J A.]]
[[Category: Putkey JA]]
[[Category: Helix-turn-helix]]
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