Specificity of blebbistatin, an inhibitor of myosin II

@article{Limouze2004SpecificityOB,
  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},
  year={2004},
  volume={25},
  pages={337-341}
}
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*

TLDR
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.

TLDR
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
TLDR
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.

TWO CLASSES OF MYOSIN INHIBITORS, BLEBBISTATIN AND MAVACAMTEN, STABILIZE β-CARDIAC MYOSIN IN DIFFERENT STRUCTURAL AND FUNCTIONAL STATES

TLDR
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

TLDR
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.

TLDR
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.

TLDR
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.

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

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