Structure-based design of a pathway-specific nuclear import inhibitor

Nat Struct Mol Biol. 2007 May;14(5):452-4. doi: 10.1038/nsmb1229. Epub 2007 Apr 15.


Kapbeta2 (also called transportin) recognizes PY nuclear localization signal (NLS), a new class of NLS with a R/H/Kx((2-5))PY motif. Here we show that Kapbeta2 complexes containing hydrophobic and basic PY-NLSs, as classified by the composition of an additional N-terminal motif, converge in structure only at consensus motifs, which explains ligand diversity. On the basis of these data and complementary biochemical analyses, we designed a Kapbeta2-specific nuclear import inhibitor, M9M.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Active Transport, Cell Nucleus / drug effects*
  • Amino Acid Motifs
  • Drug Design*
  • Karyopherins / antagonists & inhibitors*
  • Nuclear Localization Signals
  • Structure-Activity Relationship


  • Karyopherins
  • Nuclear Localization Signals

Associated data

  • PDB/2OT8