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Allosteric inhibition of kinesin-5 modulates its processive directional motility.

Publication ,  Journal Article
Kwok, BH; Kapitein, LC; Kim, JH; Peterman, EJG; Schmidt, CF; Kapoor, TM
Published in: Nature chemical biology
September 2006

Small-molecule inhibitors of kinesin-5 (refs. 1-3), a protein essential for eukaryotic cell division, represent alternatives to antimitotic agents that target tubulin. While tubulin is needed for multiple intracellular processes, the known functions of kinesin-5 are limited to dividing cells, making it likely that kinesin-5 inhibitors would have fewer side effects than do tubulin-targeting drugs. Kinesin-5 inhibitors, such as monastrol, act through poorly understood allosteric mechanisms, not competing with ATP binding. Moreover, the microscopic mechanism of full-length kinesin-5 motility is not known. Here we characterize the motile properties and allosteric inhibition of Eg5, a vertebrate kinesin-5, using a GFP fusion protein in single-molecule fluorescence assays. We find that Eg5 is a processive kinesin whose motility includes, in addition to ATP-dependent directional motion, a diffusive component not requiring ATP hydrolysis. Monastrol suppresses the directional processive motility of microtubule-bound Eg5. These data on Eg5's allosteric inhibition will impact these inhibitors' use as probes and development as chemotherapeutic agents.

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Published In

Nature chemical biology

DOI

EISSN

1552-4469

ISSN

1552-4450

Publication Date

September 2006

Volume

2

Issue

9

Start / End Page

480 / 485

Related Subject Headings

  • Xenopus laevis
  • Xenopus Proteins
  • Thiones
  • Spindle Apparatus
  • Recombinant Fusion Proteins
  • Pyrimidines
  • Microtubules
  • Microscopy, Fluorescence
  • Kinesins
  • Green Fluorescent Proteins
 

Citation

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Kwok, B. H., Kapitein, L. C., Kim, J. H., Peterman, E. J. G., Schmidt, C. F., & Kapoor, T. M. (2006). Allosteric inhibition of kinesin-5 modulates its processive directional motility. Nature Chemical Biology, 2(9), 480–485. https://doi.org/10.1038/nchembio812
Kwok, Benjamin H., Lukas C. Kapitein, Jeffrey H. Kim, Erwin J. G. Peterman, Christoph F. Schmidt, and Tarun M. Kapoor. “Allosteric inhibition of kinesin-5 modulates its processive directional motility.Nature Chemical Biology 2, no. 9 (September 2006): 480–85. https://doi.org/10.1038/nchembio812.
Kwok BH, Kapitein LC, Kim JH, Peterman EJG, Schmidt CF, Kapoor TM. Allosteric inhibition of kinesin-5 modulates its processive directional motility. Nature chemical biology. 2006 Sep;2(9):480–5.
Kwok, Benjamin H., et al. “Allosteric inhibition of kinesin-5 modulates its processive directional motility.Nature Chemical Biology, vol. 2, no. 9, Sept. 2006, pp. 480–85. Epmc, doi:10.1038/nchembio812.
Kwok BH, Kapitein LC, Kim JH, Peterman EJG, Schmidt CF, Kapoor TM. Allosteric inhibition of kinesin-5 modulates its processive directional motility. Nature chemical biology. 2006 Sep;2(9):480–485.

Published In

Nature chemical biology

DOI

EISSN

1552-4469

ISSN

1552-4450

Publication Date

September 2006

Volume

2

Issue

9

Start / End Page

480 / 485

Related Subject Headings

  • Xenopus laevis
  • Xenopus Proteins
  • Thiones
  • Spindle Apparatus
  • Recombinant Fusion Proteins
  • Pyrimidines
  • Microtubules
  • Microscopy, Fluorescence
  • Kinesins
  • Green Fluorescent Proteins