Structure-based design of a pathway-specific nuclear import inhibitor.
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.
Cansizoglu
Ahmet E
AE
Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park, Dallas, Texas 75390-9041, USA.
Lee
Brittany J
BJ
Zhang
Zi Chao
ZC
Fontoura
Beatriz M A
BM
Chook
Yuh Min
YM
D021581:Active Transport, Cell Nucleus / Q000187:drug effects*; D020816:Amino Acid Motifs; D015195:Drug Design; D028884:Karyopherins / Q000037:antagonists & inhibitors*; D019913:Nuclear Localization Signals; D013329:Structure-Activity Relationship
D028884:Karyopherins; D019913:Nuclear Localization Signals