Specificity of blebbistatin, an inhibitor of myosin II

  title={Specificity of blebbistatin, an inhibitor of myosin II},
  author={John Limouze and Aaron F. Straight and Timothy J. Mitchison and James R. Sellers},
  journal={Journal of Muscle Research \& Cell Motility},
Blebbistatin is a small molecule inhibitor discovered in a screen for inhibitors of nonmuscle myosin IIA. We have examined the specificity and potency of the drug by assaying its effects on the actin-activated MgATPase assay of diverse members of the myosin superfamily. Blebbistatin potently inhibits several striated muscle myosins as well as vertebrate nonmuscle myosin IIA and IIB with IC50 values ranging from 0.5 to 5 μM. Interestingly, smooth muscle which is highly homologous to vertebrate… 

Mechanism of Blebbistatin Inhibition of Myosin II*

The property that blebbistatin blocks myosin II in an actin-detached state makes the compound useful both in muscle physiology and in exploring the cellular function of cytoplasmic myOSin II isoforms, whereas the stabilization of a specificMyosin intermediate confers a great potential in structural studies.

Characterization of Blebbistatin Inhibition of Smooth Muscle Myosin and Nonmuscle Myosin-2.

It is found that the A456F mutation renders SmM and NM2s resistant to blebbistatin without greatly altering their motor activities or phosphorylation-dependent regulation, making A457F a useful mutant for investigating the cellular function ofNM2s.

Blebbistatin and blebbistatin-inactivated myosin II inhibit myosin II-independent processes in Dictyostelium.

  • S. ShuXiong LiuE. Korn
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 2005
It is found that blebbistatin inhibits three myosin II-dependent processes in Dictyostelium (growth in suspension culture, capping of Con A receptors, and development to fruiting bodies) and does not inhibit growth on plates, which does not require myOSin II.


It is concluded that mavacamten and blebbistatin stabilize myosin in different structural states, and such states may give rise to different functional energy-sparing SRX states.

The structural basis of blebbistatin inhibition and specificity for myosin II

The structure of blebbistatin, which inhibits specific myosin isoforms, bound to the motor domain of Dictyostelium discoideum myOSin II is reported, which reveals the structural basis for its specificity and provides insight into the development of new agents.

Blebbistatin stabilizes the helical order of myosin filaments by promoting the switch 2 closed state.

Structural observations support the conclusion, based on biochemical studies, that blebbistatin inhibits myosin ATPase and actin interaction by stabilizing the closed switch 2 structure of the myOSin head.

Small-molecule inhibitors of myosin proteins.

This review will provide a brief overview of the characteristics and scientific/therapeutic applications of the presently identified small-molecule myosin inhibitors before discussing the future of myOSin inhibitor and activator design.

Blebbistatin, a myosin II inhibitor, suppresses contraction and disrupts contractile filaments organization of skinned taenia cecum from guinea pig.

It is suggested that blebbistatin suppressed skinned smooth muscle contraction through disruption of structure of SMM by the agent.



A small-molecule inhibitor of skeletal muscle myosin II

The isolation of N-benzyl-p-toluene sulphonamide (BTS) and the recently discovered Eg5 kinesin inhibitor, monastrol, suggests that motor proteins may be potential targets for therapeutic applications.

2,3-Butanedione monoxime (BDM) as a myosin inhibitor

  • E. Ostap
  • Biology, Chemistry
    Journal of Muscle Research & Cell Motility
  • 2004
BDM has a broad effect on many non-myosin proteins (many uncharacterized), and thus should not be used in whole-cell experiments as a myosin inhibitor.

Kinetic Mechanism of Non-muscle Myosin IIB

The kinetic characterization of a human non-muscle myosin IIB subfragment-1 construct produced in the baculovirus expression system shows that most steps of the actomyosin ATPase cycle are slowed down compared with other class II myosins.

Functional Divergence of Human Cytoplasmic Myosin II

Cytoplasmic (or non-muscle) myosin II isoforms are widely expressed molecular motors playing essential cellular roles in cytokinesis and cortical tension maintenance. Two of the three human

Regulation of Class I and Class II Myosins by Heavy Chain Phosphorylation*

The existence of a myosin family presently comprising 11 classes defined by the extent of sequence homology within the subfragment-1 (S-1) domain is recognized: 10 unconventionalMyosin classes and 1 conventional (so named because it was the first to be discovered) class.

Myosin-specific adaptations of the motility assay.

Neck Length and Processivity of Myosin V*

Myosin V is an unconventional myosin that transports cargo such as vesicles, melanosomes, or mRNA on actin filaments. It is a two-headed myosin with an unusually long neck that has six IQ motifs

Baculovirus Expression of Chicken Nonmuscle Heavy Meromyosin II-B

Two truncated isoforms of chicken nonmuscle myosin II-B using the baculovirus expression system were capable of moving actin filaments in an in vitro motility assay and manifested a greater than 20-fold activation of actin-activated MgATPase activity following phosphorylation of the 20-kDa MLC.