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spinqualitylabelsall models 1dtl, resolution 2.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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 CA and BEP 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

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