7svc: Difference between revisions
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==NMR structure of cTnC-TnI chimera bound to calcium and A2== | ==NMR structure of cTnC-TnI chimera bound to calcium and A2== | ||
<StructureSection load='7svc' size='340' side='right'caption='[[7svc]]' scene=''> | <StructureSection load='7svc' size='340' side='right'caption='[[7svc]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full | <table><tr><td colspan='2'>[[7svc]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7SVC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SVC FirstGlance]. <br> | ||
</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=7svc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7svc OCA], [https://pdbe.org/7svc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7svc RCSB], [https://www.ebi.ac.uk/pdbsum/7svc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7svc ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C9W:4-(3-cyano-3-methylazetidine-1-carbonyl)-N-[(3R,4S)-7-fluoro-4-hydroxy-6-methyl-3,4-dihydro-2H-1-benzopyran-3-yl]-5-methyl-1H-pyrrole-2-sulfonamide'>C9W</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=7svc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7svc OCA], [https://pdbe.org/7svc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7svc RCSB], [https://www.ebi.ac.uk/pdbsum/7svc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7svc ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== 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> | |||
== 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. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Cardiac troponin is a regulatory protein complex located on the sarcomere that regulates the engagement of myosin on actin filaments. Low-molecular weight modulators of troponin that bind allosterically with the calcium ion have the potential to improve cardiac contractility in patients with reduced cardiac function. Here we propose an approach to the rational design of troponin modulators through the combined use of solution nuclear magnetic resonance and isothermal titration calorimetry methods. In contrast to traditional approaches limited to calcium and activator-bound troponin structures, here we analyzed the structural and thermodynamic impact of an activator in the context of the troponin functional cycle. This led us to propose a rationale for developing an efficacious troponin activator. | |||
Structural and Thermodynamic Model for the Activation of Cardiac Troponin.,Poppe L, Hartman JJ, Romero A, Reagan JD Biochemistry. 2022 Mar 29. doi: 10.1021/acs.biochem.2c00084. PMID:35349258<ref>PMID:35349258</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7svc" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Hartman | [[Category: Hartman, J J]] | ||
[[Category: Poppe L]] | [[Category: Poppe, L]] | ||
[[Category: Reagan | [[Category: Reagan, J D]] | ||
[[Category: Romero A]] | [[Category: Romero, A]] | ||
[[Category: Calcium sensitizer]] | |||
[[Category: Metal binding protein]] | |||
Latest revision as of 13:22, 13 April 2022
NMR structure of cTnC-TnI chimera bound to calcium and A2NMR structure of cTnC-TnI chimera bound to calcium and A2
Structural highlights
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. Publication Abstract from PubMedCardiac troponin is a regulatory protein complex located on the sarcomere that regulates the engagement of myosin on actin filaments. Low-molecular weight modulators of troponin that bind allosterically with the calcium ion have the potential to improve cardiac contractility in patients with reduced cardiac function. Here we propose an approach to the rational design of troponin modulators through the combined use of solution nuclear magnetic resonance and isothermal titration calorimetry methods. In contrast to traditional approaches limited to calcium and activator-bound troponin structures, here we analyzed the structural and thermodynamic impact of an activator in the context of the troponin functional cycle. This led us to propose a rationale for developing an efficacious troponin activator. Structural and Thermodynamic Model for the Activation of Cardiac Troponin.,Poppe L, Hartman JJ, Romero A, Reagan JD Biochemistry. 2022 Mar 29. doi: 10.1021/acs.biochem.2c00084. PMID:35349258[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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