Cardiac muscle myosin heavy chain 7 (MYH7)

Cardiac muscle myosin heavy chain 7 (MYH7), often referred to by its enzymatic activity as Myosin ATPase, is the primary motor protein responsible for generating force in the human heart. It functions as an allosteric enzyme that converts chemical energy from ATP hydrolysis into mechanical work through a complex chemo-mechanical cycle [4, 19]. This cycle involves the binding of ATP, its hydrolysis to ADP and inorganic phosphate (Pi), and the subsequent release of Pi, which triggers the 'power stroke' and the transition of myosin heads from a weak to a strong actin-binding state [2, 10]. In healthy tissue, a significant portion of myosin heads exists in a 'super-relaxed' (SRX) state—an energy-sparing conformation with extremely slow ATP turnover that provides a functional reserve for recruitment during physical exertion [5, 12]. Dysregulation of Myosin ATPase activity is a central driver in various cardiomyopathies. In hypertrophic cardiomyopathy (HCM), mutations often destabilize the SRX state, leading to hypercontractility and impaired relaxation, which can cause left ventricular outflow tract (LVOT) obstruction [7, 17]. Therapeutic agents such as Mavacamten and Aficamten have been developed to bind allosterically to the myosin head, inhibiting ATPase activity and stabilizing the SRX state to reduce hypercontractility [1, 6]. Conversely, in heart failure with reduced ejection fraction (HFrEF), activators like omecamtiv mecarbil aim to enhance systolic function by increasing the number of myosin heads entering the force-producing state [3, 15]. Clinical use of these modulators requires careful monitoring of biomarkers like NT-proBNP and left ventricular ejection fraction (LVEF) to avoid the risk of excessive systolic dysfunction or heart failure [5, 22].

Other names

Beta-myosin heavy chainMyosin-7Cardiac myosin ATPaseMyosin heavy chain 7Slow/cardiac muscle myosin heavy chainMYH7

Allosteric modulation of the myosin catalytic domain to regulate the ATPase cycle; inhibitors typically slow phosphate release or stabilize the super-relaxed (SRX) state, while activators accelerate the transition to the force-producing state.