Myosin superfamily (MYO)

The myosin superfamily comprises a diverse group of ATP-dependent motor proteins that move along actin filaments to generate mechanical force and movement in eukaryotic cells (UniProt). These proteins are characterized by a conserved catalytic head domain that binds actin and hydrolyzes ATP, a neck region that acts as a lever arm, and a tail domain that determines cargo specificity or filament assembly (Wikipedia). Myosins are categorized into numerous classes, with Myosin II being the primary driver of muscle contraction and cytokinesis, while unconventional myosins like Myosin V and VI facilitate intracellular transport and sensory functions (PubMed: 10677020). Mutations in various myosin genes are implicated in a wide range of human pathologies, most notably hypertrophic and dilated cardiomyopathies, as well as hereditary deafness and cancer progression (NIH/StatPearls). In modern pharmacology, cardiac myosins have emerged as critical therapeutic targets; small-molecule inhibitors are utilized to treat obstructive hypertrophic cardiomyopathy by reducing hypercontractility, while myosin activators are being investigated to enhance cardiac output in patients with heart failure (PubChem).

Other names

Myosin proteinsActin-based motor proteinsMolecular motorsMyosin ATPase

Drugs targeting the myosin superfamily typically act as allosteric modulators of the myosin ATPase cycle. Inhibitors like mavacamten stabilize the 'super-relaxed' state of cardiac myosin, reducing the number of myosin heads available for power strokes and decreasing contractility (PubMed: 31558438). Conversely, activators like omecamtiv mecarbil increase the rate of phosphate release, accelerating the transition to the force-generating state and prolonging the duration of ejection without increasing intracellular calcium (PubMed: 21248130).