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基于结构的特定信号通路核输入抑制剂设计

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

作者信息

Cansizoglu Ahmet E, Lee Brittany J, Zhang Zi Chao, Fontoura Beatriz M A, Chook Yuh Min

机构信息

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

出版信息

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

DOI:10.1038/nsmb1229
PMID:17435768
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3437620/
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.

摘要

Kapβ2(也称为转运蛋白)识别PY核定位信号(NLS),这是一类新的具有R/H/Kx((2-5))PY基序的NLS。我们在此表明,根据额外N端基序的组成分类,含有疏水和碱性PY-NLS的Kapβ2复合物仅在共有基序处结构趋同,这解释了配体多样性。基于这些数据和补充生化分析,我们设计了一种Kapβ2特异性核输入抑制剂M9M。

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本文引用的文献

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Rules for nuclear localization sequence recognition by karyopherin beta 2.核转运蛋白β2识别核定位序列的规则。
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Two motifs essential for nuclear import of the hnRNP A1 nucleocytoplasmic shuttling sequence M9 core.对于核不均一核糖核蛋白A1核质穿梭序列M9核心的核输入至关重要的两个基序。
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