Smooth muscle myosin II (SMM II)

Smooth muscle myosin II is a hexameric molecular motor protein essential for the contraction of smooth muscle cells found in the walls of hollow organs, such as blood vessels, the gastrointestinal tract, and the respiratory airways (1.1.2, 1.4.2). It consists of two heavy chains, typically Myosin-11 (MYH11), and two pairs of light chains that regulate its ATPase activity and force generation (1.2.2, 1.2.3). The primary biological function of this protein is to convert chemical energy from ATP hydrolysis into mechanical work, driving the sliding of actin filaments and resulting in muscle shortening (1.1.2, 1.4.5). In various diseases, such as hypertension and asthma, hypercontractility of smooth muscle leads to pathological narrowing of vessels or airways, making smooth muscle myosin II an attractive therapeutic target (1.3.1, 1.3.2). Direct inhibitors of this motor protein, such as CK-2018448 and CK-2018571, aim to induce muscle relaxation by blocking the cross-bridge cycle without affecting upstream calcium signaling (1.3.1, 1.3.2). While these agents offer a novel approach to treating hypercontractile states, achieving selectivity over cardiac and skeletal myosin isoforms remains a significant challenge to avoid systemic side effects (1.3.3). Additionally, circulating levels of smooth muscle myosin heavy chains serve as important clinical biomarkers for conditions like acute aortic dissection (1.5.3).

Other names

Smooth muscle myosinMyosin-11MYH11Conventional smooth muscle myosinSMM

Direct inhibition of the myosin ATPase activity and actin-binding, trapping the motor in a non-force-producing intermediate state of the recovery stroke to prevent cross-bridge cycling.