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2kfx

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Revision as of 10:51, 18 July 2018

Structure of the N-terminal domain of human cardiac troponin C bound to calcium ion and to the inhibitor W7

Structural highlights

2kfx is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	TNNC1, TNNC (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[TNNC1_HUMAN] Defects in TNNC1 are the cause of cardiomyopathy dilated type 1Z (CMD1Z) [MIM: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.^[1] Defects in TNNC1 are the cause of familial hypertrophic cardiomyopathy type 13 (CMH13) [MIM: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.^[2] ^[3] ^[4] ^[5]

Function

[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

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The calmodulin antagonist W7 binds to troponin C in the presence of Ca(2+) and inhibits striated muscle contraction. This study integrates multiple data into the structure of the regulatory domain of human cardiac troponin C (cNTnC) bound to Ca(2+) and W7. The protein-W7 interface is defined through a three-dimensional {(1)H,(13)C}-edited-{(1)H,(12)C}-detected NOESY NMR experiment, and other aspects of the structure are modeled as perturbations to previously known coordinates and restraints. The structure determination protocol optimizes the protein-W7 contacts prior to the introduction of protein-W7 steric interactions or conformational changes in the protein. The structure determination protocol gives families of conformers that all have an optimal docking as assessed by satisfaction of the target function. The structure supports the previously proposed troponin I blocking mechanism for the activity of W7 in striated muscle and suggests a role for the flexible tail of W7 in stabilization of the bound state. This clarifies the structure-activity relationships of W7 and implicates an electrostatically mediated component of activity in common analogues of W7, including the antipsychotic trifluoroperazine and the cardiotonic levosimendan.

Structure of the Inhibitor W7 Bound to the Regulatory Domain of Cardiac Troponin C.,Hoffman RM, Sykes BD Biochemistry. 2009 May 21. PMID:19419198^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Mogensen J, Murphy RT, Shaw T, Bahl A, Redwood C, Watkins H, Burke M, Elliott PM, McKenna WJ. Severe disease expression of cardiac troponin C and T mutations in patients with idiopathic dilated cardiomyopathy. J Am Coll Cardiol. 2004 Nov 16;44(10):2033-40. PMID:15542288 doi:S0735-1097(04)01700-0
↑ Hoffmann B, Schmidt-Traub H, Perrot A, Osterziel KJ, Gessner R. First mutation in cardiac troponin C, L29Q, in a patient with hypertrophic cardiomyopathy. Hum Mutat. 2001 Jun;17(6):524. PMID:11385718 doi:10.1002/humu.1143
↑ Schmidtmann A, Lindow C, Villard S, Heuser A, Mugge A, Gessner R, Granier C, Jaquet K. Cardiac troponin C-L29Q, related to hypertrophic cardiomyopathy, hinders the transduction of the protein kinase A dependent phosphorylation signal from cardiac troponin I to C. FEBS J. 2005 Dec;272(23):6087-97. PMID:16302972 doi:10.1111/j.1742-4658.2005.05001.x
↑ Landstrom AP, Parvatiyar MS, Pinto JR, Marquardt ML, Bos JM, Tester DJ, Ommen SR, Potter JD, Ackerman MJ. Molecular and functional characterization of novel hypertrophic cardiomyopathy susceptibility mutations in TNNC1-encoded troponin C. J Mol Cell Cardiol. 2008 Aug;45(2):281-8. doi: 10.1016/j.yjmcc.2008.05.003. Epub , 2008 May 11. PMID:18572189 doi:10.1016/j.yjmcc.2008.05.003
↑ Pinto JR, Parvatiyar MS, Jones MA, Liang J, Ackerman MJ, Potter JD. A functional and structural study of troponin C mutations related to hypertrophic cardiomyopathy. J Biol Chem. 2009 Jul 10;284(28):19090-100. doi: 10.1074/jbc.M109.007021. Epub, 2009 May 12. PMID:19439414 doi:10.1074/jbc.M109.007021
↑ Hoffman RM, Sykes BD. Structure of the Inhibitor W7 Bound to the Regulatory Domain of Cardiac Troponin C. Biochemistry. 2009 May 21. PMID:19419198 doi:10.1021/bi9001826

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2kfx"

@@ Line 1: / Line 1: @@
 ==Structure of the N-terminal domain of human cardiac troponin C bound to calcium ion and to the inhibitor W7==
 <StructureSection load='2kfx' size='340' side='right' caption='[[2kfx]], [[NMR_Ensembles_of_Models | 10 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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=WW7:N-(6-AMINOHEXYL)-5-CHLORO-1-NAPHTHALENESULFONAMIDE'>WW7</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TNNC1, 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=2kfx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kfx OCA], [http://pdbe.org/2kfx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2kfx RCSB], [http://www.ebi.ac.uk/pdbsum/2kfx 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=2kfx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kfx OCA], [http://pdbe.org/2kfx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2kfx RCSB], [http://www.ebi.ac.uk/pdbsum/2kfx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2kfx ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 15: / Line 16: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kf/2kfx_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kf/2kfx_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 40: / Line 41: @@
 [[Category: Hoffman, R M.B]]
 [[Category: Sykes, B D]]
+[[Category: Acetylation]]
+[[Category: Calcium]]
 [[Category: Calcium regulation]]
 [[Category: Cardiac]]
@@ Line 47: / Line 50: @@
 [[Category: Metal binding protein]]
 [[Category: Muscle protein]]
+[[Category: Polymorphism]]
 [[Category: Striated muscle]]
 [[Category: Troponin]]
 [[Category: W7]]

2kfx

From Proteopedia

Revision as of 10:51, 18 July 2018

Structure of the N-terminal domain of human cardiac troponin C bound to calcium ion and to the inhibitor W7

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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