Chemical Genetics Approach to Engineer Kinesins with Sensitivity towards a Small-Molecule Inhibitor of Eg5

Möckel, Martin M.; Hund, Corinna; Mayer, Thomas U.

Chemical Genetics Approach to Engineer Kinesins with Sensitivity towards a Small-Molecule Inhibitor of Eg5

Dateien

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Datum

2016

Autor:innen

Möckel, Martin M.

Hund, Corinna

Mayer, Thomas U.

Open Access-Veröffentlichung

Open Access Green

Sammlungen

Biologie

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

ChemBioChem. 2016, 17(21), pp. 2042-2045. ISSN 1439-4227. eISSN 1439-7633. Available under: doi: 10.1002/cbic.201600451

Zusammenfassung

Due to their fast and often reversible mode of action, small molecules are ideally suited to dissect biological processes. Yet, the validity of small-molecule studies is intimately tied to the specificity of the applied compounds, thus imposing a great challenge to screens for novel inhibitors. Here, we applied a chemical-genetics approach to render kinesin motor proteins sensitive to inhibition by the well-characterized small molecule S-Trityl-l-cysteine (STLC). STLC specifically inhibits the kinesin Eg5 through binding to a known allosteric site within the motor domain. Transfer of this allosteric binding site into the motor domain of the human kinesins Kif3A and Kif4A sensitizes them towards STLC. Single-molecule microscopy analyses confirmed that STLC inhibits the movement of chimeric but not wild-type Kif4A along microtubules. Thus, our proof-of-concept study revealed that this chemical-genetic approach provides a powerful strategy to specifically inhibit kinesins in vitro for which small-molecule inhibitors are not yet available.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Zitieren

ISO 690

MÖCKEL, Martin M., Corinna HUND, Thomas U. MAYER, 2016. Chemical Genetics Approach to Engineer Kinesins with Sensitivity towards a Small-Molecule Inhibitor of Eg5. In: ChemBioChem. 2016, 17(21), pp. 2042-2045. ISSN 1439-4227. eISSN 1439-7633. Available under: doi: 10.1002/cbic.201600451

BibTex

@article{Mockel2016-11-03Chemi-36992,
  year={2016},
  doi={10.1002/cbic.201600451},
  title={Chemical Genetics Approach to Engineer Kinesins with Sensitivity towards a Small-Molecule Inhibitor of Eg5},
  number={21},
  volume={17},
  issn={1439-4227},
  journal={ChemBioChem},
  pages={2042--2045},
  author={Möckel, Martin M. and Hund, Corinna and Mayer, Thomas U.}
}

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