1dtl
From Proteopedia
(New page: 200px<br /><applet load="1dtl" size="450" color="white" frame="true" align="right" spinBox="true" caption="1dtl, resolution 2.15Å" /> '''CRYSTAL STRUCTURE OF...) |
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| - | [[Image:1dtl.gif|left|200px]]<br /><applet load="1dtl" size=" | + | [[Image:1dtl.gif|left|200px]]<br /><applet load="1dtl" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1dtl, resolution 2.15Å" /> | caption="1dtl, resolution 2.15Å" /> | ||
'''CRYSTAL STRUCTURE OF CALCIUM-SATURATED (3CA2+) CARDIAC TROPONIN C COMPLEXED WITH THE CALCIUM SENSITIZER BEPRIDIL AT 2.15 A RESOLUTION'''<br /> | '''CRYSTAL STRUCTURE OF CALCIUM-SATURATED (3CA2+) CARDIAC TROPONIN C COMPLEXED WITH THE CALCIUM SENSITIZER BEPRIDIL AT 2.15 A RESOLUTION'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Cardiac troponin C (cTnC) is the calcium-dependent switch for contraction | + | 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== | ==About this Structure== | ||
| - | 1DTL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] with CA and BEP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1DTL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=BEP:'>BEP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DTL OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Cohen, C.]] | [[Category: Cohen, C.]] | ||
[[Category: Li, Y.]] | [[Category: Li, Y.]] | ||
| - | [[Category: Love, M | + | [[Category: Love, M L.]] |
| - | [[Category: Putkey, J | + | [[Category: Putkey, J A.]] |
[[Category: BEP]] | [[Category: BEP]] | ||
[[Category: CA]] | [[Category: CA]] | ||
[[Category: helix-turn-helix]] | [[Category: helix-turn-helix]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:20:19 2008'' |
Revision as of 10:20, 21 February 2008
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CRYSTAL STRUCTURE OF CALCIUM-SATURATED (3CA2+) CARDIAC TROPONIN C COMPLEXED WITH THE CALCIUM SENSITIZER BEPRIDIL AT 2.15 A RESOLUTION
Overview
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
1DTL is a Single protein structure of sequence from Gallus gallus with and as ligands. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 12:20:19 2008
Categories: Gallus gallus | Single protein | Cohen, C. | Li, Y. | Love, M L. | Putkey, J A. | BEP | CA | Helix-turn-helix
