Abstract
The calmodulin antagonist W7 is a direct sarcomere inhibitor that has therapeutic potential for the treatment of hypertrophic and restrictive cardiomyopathy. W7 decreases the calcium sensitivity of force development in cardiac muscle by binding to troponin, the sarcomere thin filament protein that regulates heart muscle contraction. W7 binds to the interface of the regulatory N-terminal domain of cardiac troponin C (cNTnC) and the switch region of troponin I (cTnI), and decreases the binding of cTnI to cNTnC presumably by electrostatic repulsion between W7 and cTnI.
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