Mechanism of Blebbistatin Inhibition of Myosin II*
By M. Kovács, J. Tóth, C. Hetényi, A. Málnási-Csizmadia, J. Sellers. Journal of Biological Chemistry, 2004
1,023 citations recorded by the source corpus.
Blebbistatin is a recently discovered small molecule inhibitor showing high affinity and selectivity toward myosin II. Here we report a detailed investigation of its mechanism of inhibition. Blebbistatin does not compete with nucleotide binding to the skeletal muscle myosin subfragment-1. The inhibitor preferentially binds to the ATPase intermediate with ADP and phosphate bound at the active site, and it slows down phosphate release. Blebbistatin interferes neither with binding of myosin to actin nor with ATP-induced actomyosin dissociation. Instead, it blocks the myosin heads in a products complex with low actin affinity. Blind docking molecular simulations indicate that the productive blebbistatin-binding site of the myosin head is within the aqueous cavity between the nucleotide pocket and the cleft of the actin-binding interface. 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 specific myosin intermediate confers a great potential in structural studies.
Subfields: Cardiology and Cardiovascular Medicine, Cell Biology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/a728659ef487f713d97ebd18a93eee5cc3373ffc
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In Cardiology and Cardiovascular Medicine
In Cell Biology
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Citations in the corpus
- Author Manuscript (2013, background): “Blebbistatin is a cell-permeant molecule that functionally blocks myosin II in an actin detached state [21].”
- Mechanical compression drives cancer cells toward invasive phenotype (2011, background): “Interestingly, when actomyosin contractility was completely blocked by the myosin II ATPase inhibitor Blebbistatin (35), compressive stress was still able to induce leader-cell formation despite compromised cell motility (Fig.”