Fast skeletal muscle myosin-2 (SkMII)

Fast skeletal muscle myosin-2 is a specialized motor protein found in type II muscle fibers, responsible for rapid force generation and high-velocity contraction (UniProt, PMC4916140). It functions as an ATPase, utilizing energy from ATP to drive the sliding of actin filaments within the sarcomere (PubMed 11784865). This protein is a critical therapeutic target in muscular dystrophies, such as Duchenne and Becker muscular dystrophy, where reducing the mechanical stress of contraction can prevent fiber damage and slow disease progression (Edgewise Therapeutics, PMC8544410). Small molecule inhibitors like sevasemten (EDG-5506) selectively target this isoform to stabilize the sarcomere without affecting cardiac or slow-twitch muscle function (PMC8544410). Additionally, research into myosin modulators extends to conditions involving muscle hypercontractility and spasticity, highlighting its central role in neuromuscular health and disease (MotorPharma, PNAS 113.47).

Other names

Fast skeletal myosinFast-twitch skeletal muscle myosin IIType II myosinSkeletal muscle myosin IIMYH1MYH2MYH4

Selective allosteric inhibition of the fast skeletal muscle myosin II ATPase activity, which stabilizes the myosin-ADP-Pi complex in a weak actin-binding state, thereby reducing force production and mechanical stress on the sarcomere.