β-cardiac myosin S1 domain

The β-cardiac myosin S1 domain is the **catalytic and motor head region** of human cardiac myosin, encoded by the MYH7 gene, and is responsible for generating force and movement in cardiac muscle through ATP hydrolysis and actin binding[1][2][4][8]. The S1 domain contains an **N-terminal motor domain** that binds to actin and ATP/ADP, producing a power stroke essential for cardiac contraction. Structural studies indicate this domain’s conformation and interactions are finely regulated, with specific sites serving as hotspots for disease-causing mutations, especially hypertrophic cardiomyopathy (HCM), where S1 domain mutations change contractile properties, leading to disease[1][2][4][6][8]. The β-cardiac myosin S1 domain is the direct molecular target of **small-molecule modulators** such as **omecamtiv mecarbil** (which increases contractility) and **mavacamten** (which reduces hypercontractility in HCM), marking it as a major therapeutic target for cardiomyopathies and heart failure[3][6]. Its three-dimensional structure has been resolved by crystallography and cryo-EM, and its interactions with small molecules are conformational-state dependent, underlining its therapeutic and pathophysiological significance[1][3][5][6].

Other names

beta-cardiac myosin S1 domainβ-cardiac myosin S1 headhuman β-cardiac myosin subfragment-1 (sS1)MYH7 motor domain (when referring specifically to the heavy chain protein)

Allosteric modulation of myosin ATPase activity and contractility (e.g., omecamtiv mecarbil activates myosin, mavacamten inhibits hypercontractile mutations)[3].