DHTP is an allosteric inhibitor of the kinesin-13 family of microtubule depolymerases

FEBS Lett. 2014 Jun 27;588(14):2315-20. doi: 10.1016/j.febslet.2014.05.024. Epub 2014 May 22.

Abstract

The kinesin-13 family of microtubule depolymerases is a major regulator of microtubule dynamics. RNA interference-induced knockdown studies have highlighted their importance in many cell division processes including spindle assembly and chromosome segregation. Since microtubule turnovers and most mitotic events are relatively rapid (in minutes or seconds), developing tools that offer faster control over protein functions is therefore essential to more effectively interrogate kinesin-13 activities in living cells. Here, we report the identification and characterization of a selective allosteric kinesin-13 inhibitor, DHTP. Using high resolution microscopy, we show that DHTP is cell permeable and can modulate microtubule dynamics in cells.

Keywords: Cell division; Chemical inhibitor; Enzyme; Kinesin; Microtubule.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / chemistry
  • Adenosine Triphosphate / chemistry
  • Allosteric Regulation
  • Animals
  • Cattle
  • Drug Evaluation, Preclinical
  • Humans
  • Kinesins / antagonists & inhibitors*
  • Kinesins / chemistry
  • Microtubules / chemistry
  • Protein Multimerization
  • Pyrimidines / chemistry*
  • Thiazolidines / chemistry*
  • Tubulin Modulators / chemistry*

Substances

  • 2-(4-((5-(4-chlorophenyl)-6-(isopropoxycarbonyl)-7-methyl-3-oxo-3,5-dihydro-2H-thiazolo(3,2-a)pyrimidin-2-ylidene)methyl)phenoxy)acetic acid
  • KIF13A protein, human
  • Pyrimidines
  • Thiazolidines
  • Tubulin Modulators
  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • Kinesins