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

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

Author information

1
Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park, Dallas, Texas 75390-9041, USA.

Abstract

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.

PMID:
17435768
PMCID:
PMC3437620
DOI:
10.1038/nsmb1229
[Indexed for MEDLINE]
Free PMC Article

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