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The structural basis of blebbistatin inhibition and specificity for myosin II

Nature Structural & Molecular Biology volume 12, pages 378–379 (2005)Cite this article

Abstract

Molecular motors play a central role in cytoskeletal-mediated cellular processes and thus present an excellent target for cellular control by pharmacological agents. Yet very few such compounds have been found. We report here the structure of blebbistatin, which inhibits specific myosin isoforms, bound to the motor domain of Dictyostelium discoideum myosin II. This reveals the structural basis for its specificity and provides insight into the development of new agents.

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Figure 1: Blebbistatin chemical structure and binding site on MgADP–vanadate myosin II.
Figure 2: Blebbistatin-binding site and contact residue conservation for different myosin isoforms.

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Acknowledgements

We thank V. Klenchin and M. St. Maurice for helpful discussions and C. Grutzmacher for technical assistance. This work was supported by a fellowship to J.S.A. from the Canadian Institutes of Health Research (64606) and a research grant to I.R. from the US National Institutes of Health (AR35186). Use of the LS-CAT beamline at Argonne National Laboratory Advanced Photon Source was supported by the US Department of Energy, Office of Energy Research, under contract no. W-31-109-ENG-38.

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Authors and Affiliations

  1. Department of Biochemistry, University of Wisconsin, 433 Babcock Drive, Madison, 53706, Wisconsin, USA

    John S Allingham, Robert Smith & Ivan Rayment

Authors
  1. John S Allingham
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  2. Robert Smith
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  3. Ivan Rayment
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Correspondence to Ivan Rayment.

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Supplementary information

Supplementary Fig. 1

Stereo view of electron density for blebbistatin bound to Dictyostelium discoideum myosin S1dC. (PDF 625 kb)

Supplementary Fig. 2

Stereo view of apo and blebbistatin-bound forms of S1dC. (PDF 710 kb)

Supplementary Fig. 3

Inhibition of S1dC by blebbistatin. (PDF 57 kb)

Supplementary Table 1

Data collection and refinement statistics for the structural analysis. (PDF 71 kb)

Supplementary Methods (PDF 39 kb)

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Allingham, J., Smith, R. & Rayment, I. The structural basis of blebbistatin inhibition and specificity for myosin II. Nat Struct Mol Biol 12, 378–379 (2005). https://doi.org/10.1038/nsmb908

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