Structure-based design of a pathway-specific nuclear import inhibitor |
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Authors: | Cansizoglu Ahmet E Lee Brittany J Zhang Zi Chao Fontoura Beatriz M A Chook Yuh Min |
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Affiliation: | Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park, Dallas, Texas 75390-9041, USA. |
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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. |
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