1dtl

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[[Image:1dtl.gif|left|200px]]
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{{STRUCTURE_1dtl| PDB=1dtl | SCENE= }}
{{STRUCTURE_1dtl| PDB=1dtl | SCENE= }}
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'''CRYSTAL STRUCTURE OF CALCIUM-SATURATED (3CA2+) CARDIAC TROPONIN C COMPLEXED WITH THE CALCIUM SENSITIZER BEPRIDIL AT 2.15 A RESOLUTION'''
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===CRYSTAL STRUCTURE OF CALCIUM-SATURATED (3CA2+) CARDIAC TROPONIN C COMPLEXED WITH THE CALCIUM SENSITIZER BEPRIDIL AT 2.15 A RESOLUTION===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 10792039 is the PubMed ID number.
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{{ABSTRACT_PUBMED_10792039}}
==About this Structure==
==About this Structure==
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[[Category: Putkey, J A.]]
[[Category: Putkey, J A.]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 23:35:50 2008''

Revision as of 20:35, 30 June 2008

Image:1dtl.png

Template:STRUCTURE 1dtl

CRYSTAL STRUCTURE OF CALCIUM-SATURATED (3CA2+) CARDIAC TROPONIN C COMPLEXED WITH THE CALCIUM SENSITIZER BEPRIDIL AT 2.15 A RESOLUTION

Template:ABSTRACT PUBMED 10792039

About this Structure

1DTL is a Single protein structure of sequence from Gallus gallus. 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

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