1ih0
From Proteopedia
(New page: 200px<br /> <applet load="1ih0" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ih0" /> '''Structure of the C-domain of Human Cardiac ...) |
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'''Structure of the C-domain of Human Cardiac Troponin C in Complex with Ca2+ Sensitizer EMD 57033'''<br /> | '''Structure of the C-domain of Human Cardiac Troponin C in Complex with Ca2+ Sensitizer EMD 57033'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1IH0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA and EMD as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1IH0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=EMD:'>EMD</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IH0 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: ca2+ sensitizer]] | [[Category: ca2+ sensitizer]] | ||
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Revision as of 14:01, 15 February 2008
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Structure of the C-domain of Human Cardiac Troponin C in Complex with Ca2+ Sensitizer EMD 57033
Contents |
Overview
Ca(2+) binding to cardiac troponin C (cTnC) triggers contraction in heart, muscle. In heart failure, myofilaments response to Ca(2+) are often, altered and compounds that sensitize the myofilaments to Ca(2+) possess, therapeutic value in this syndrome. One of the most potent and selective, Ca(2+) sensitizers is the thiadiazinone derivative EMD 57033, which, increases myocardial contractile function both in vivo and in vitro and, interacts with cTnC in vitro. We have determined the NMR structure of the, 1:1 complex between Ca(2+)-saturated C-domain of human cTnC (cCTnC) and, EMD 57033. Favorable hydrophobic interactions between the drug and the, protein position EMD 57033 in the hydrophobic cleft of the protein. The, drug molecule is orientated such that the chiral group of EMD 57033 fits, deep in the hydrophobic pocket and makes several key contacts with the, protein. This stereospecific interaction explains why the (-)-enantiomer, of EMD 57033 is inactive. Titrations of the cCTnC.EMD 57033 complex with, two regions of cardiac troponin I (cTnI(34-71) and cTnI(128-147)) reveal, that the drug does not share a common binding epitope with cTnI(128-147), but is completely displaced by cTnI(34-71). These results have important, implications for elucidating the mechanism of the Ca(2+) sensitizing, effect of EMD 57033 in cardiac muscle contraction.
Disease
Known diseases associated with this structure: Cardiomyopathy, familial hypertrophic, 192600 (3) OMIM:[191040]
About this Structure
1IH0 is a Single protein structure of sequence from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
Reference
Structure of the C-domain of human cardiac troponin C in complex with the Ca2+ sensitizing drug EMD 57033., Wang X, Li MX, Spyracopoulos L, Beier N, Chandra M, Solaro RJ, Sykes BD, J Biol Chem. 2001 Jul 6;276(27):25456-66. Epub 2001 Apr 24. PMID:11320096
Page seeded by OCA on Fri Feb 15 16:01:17 2008
Categories: Homo sapiens | Single protein | Beier, N. | Chandra, M. | Li, M.X. | Solaro, R.J. | Spyracopoulos, L. | Sykes, B.D. | Wang, X. | CA | EMD | Ca2+ binding protein | Ca2+ sensitizer
