1DTL

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

Summary for 1DTL

• Entry DOI: 10.2210/pdb1dtl/pdb
• Descriptor: CARDIAC TROPONIN C, CALCIUM ION, 1-ISOBUTOXY-2-PYRROLIDINO-3[N-BENZYLANILINO] PROPANE, ... (4 entities in total)
• Functional Keywords: helix-turn-helix, structural protein
• Biological source: Gallus gallus (chicken)
• Total number of polymer chains: 1
• Total formula weight: 19621.23

Authors

Li, Y.,Love, M.L.,Putkey, J.A.,Cohen, C. (deposition date: 2000-01-12, release date: 2000-05-12, Last modification date: 2023-08-09)

Primary citation

Li, Y.,Love, M.L.,Putkey, J.A.,Cohen, C.
Bepridil opens the regulatory N-terminal lobe of cardiac troponin C.
Proc.Natl.Acad.Sci.USA, 97:5140-5145, 2000

PubMed Abstract: 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.

PubMed: 10792039
DOI: 10.1073/pnas.090098997

Experimental method

X-RAY DIFFRACTION (2.15 Å)