Actomyosin magnesium-dependent adenosine triphosphatase (Actomyosin Mg2+-ATPase)

Actomyosin magnesium-dependent adenosine triphosphatase (Actomyosin Mg2+-ATPase) is the enzymatic complex responsible for converting chemical energy from ATP into mechanical force within muscle and non-muscle cells. This activity occurs when the myosin motor head binds to actin filaments, significantly accelerating the rate of ATP hydrolysis compared to myosin alone (PubMed: 3150334). In cardiac and skeletal muscles, this process drives the cross-bridge cycle, which is the fundamental mechanism of contraction and force production (UniProt: P12883). Pathological alterations in the kinetics of this ATPase activity are central to various cardiovascular diseases; for example, mutations that increase ATPase activity often lead to hypertrophic cardiomyopathy, while decreased activity is associated with dilated cardiomyopathy and heart failure (PubMed: 26365312). Modern pharmacology has targeted this enzyme complex with small-molecule modulators: cardiac myosin inhibitors like Mavacamten reduce the ATPase rate to treat obstructive hypertrophic cardiomyopathy, whereas cardiac myosin activators like Omecamtiv mecarbil enhance the transition to the force-generating state to improve cardiac output in heart failure (PubMed: 32433836). These drugs typically bind to allosteric sites on the myosin head, altering the kinetics of the cross-bridge cycle without directly affecting calcium signaling.

Other names

Actin-activated myosin ATPaseMyosin ATPaseMagnesium-dependent actomyosin ATPaseCardiac actomyosin ATPase

Allosteric modulation of the myosin motor head to regulate the rate-limiting steps of the ATP hydrolysis cycle and the transition between weak and strong actin-binding states.