7kaa: Difference between revisions
New page: '''Unreleased structure''' The entry 7kaa is ON HOLD Authors: Mercier, P., Li, M.X., Hartman, J.J., Sykes, B.D. Description: NMR solution structures of tirasemtiv drug bound to a fast ... |
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The entry | ==NMR solution structures of tirasemtiv drug bound to a fast skeletal troponin C-troponin I complex== | ||
<StructureSection load='7kaa' size='340' side='right'caption='[[7kaa]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7kaa]] is a 1 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=7KAA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KAA FirstGlance]. <br> | |||
</td></tr><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=W97:6-ethynyl-1-(pentan-3-yl)-1H-imidazo[4,5-b]pyrazin-2-ol'>W97</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=7kaa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kaa OCA], [https://pdbe.org/7kaa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kaa RCSB], [https://www.ebi.ac.uk/pdbsum/7kaa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kaa ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/TNNI2_HUMAN TNNI2_HUMAN] Sheldon-Hall syndrome;Digitotalar dysmorphism. The disease is caused by mutations affecting the gene represented in this entry. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/TNNC2_HUMAN TNNC2_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.[https://www.uniprot.org/uniprot/TNNI2_HUMAN TNNI2_HUMAN] Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Troponin regulates the calcium-mediated activation of skeletal muscle. Muscle weakness in diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy occurs from diminished neuromuscular output. The first direct fast skeletal troponin activator, tirasemtiv, amplifies the response of muscle to neuromuscular input. Tirasemtiv binds selectively and strongly to fast skeletal troponin, slowing the rate of calcium release and sensitizing muscle to calcium. We report the solution NMR structure of tirasemtiv bound to a fast skeletal troponin C-troponin I chimera. The structure reveals that tirasemtiv binds in a hydrophobic pocket between the regulatory domain of troponin C and the switch region of troponin I, which overlaps with that of Anapoe in the X-ray structure of skeletal troponin. Multiple interactions stabilize the troponin C-troponin I interface, increase the affinity of troponin C for the switch region of fast skeletal troponin I, and drive the equilibrium toward the active state. | |||
Structural Basis of Tirasemtiv Activation of Fast Skeletal Muscle.,Li MX, Mercier P, Hartman JJ, Sykes BD J Med Chem. 2021 Mar 11. doi: 10.1021/acs.jmedchem.0c01412. PMID:33703886<ref>PMID:33703886</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7kaa" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Troponin 3D structures|Troponin 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Hartman JJ]] | |||
[[Category: Li MX]] | |||
[[Category: Mercier P]] | |||
[[Category: Sykes BD]] | |||