支化三泛素活性位点导向探针的合成。
Synthesis of Branched Triubiquitin Active-Site Directed Probes.
机构信息
Department of Chemistry, University of Massachusetts, Amherst, Massachusetts 01003, United States.
Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, Massachusetts 01003, United States.
出版信息
Org Lett. 2019 Sep 6;21(17):6790-6794. doi: 10.1021/acs.orglett.9b02406. Epub 2019 Aug 9.
Abstract
Active-site directed probes are powerful tools for studying the ubiquitin conjugation and deconjugation machinery. Branched ubiquitin chains have emerged as important proteasome-targeting signals for aggregation-prone proteins and cell cycle regulators. By implementing a new synthetic strategy for the electrophilic warhead, we herein report on the generation and reactivity of a series of branched triubiquitin active-site directed probes. These new tools can be used to dissect the molecular basis of branched chain assembly and disassembly.
摘要
活性位点导向探针是研究泛素缀合和解离机制的有力工具。支化泛素链已成为聚集倾向蛋白和细胞周期调节剂的重要蛋白酶体靶向信号。通过实施新的亲电弹头合成策略，我们在此报告了一系列支化三泛素活性位点导向探针的生成和反应性。这些新工具可用于剖析支化链组装和拆卸的分子基础。
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本文引用的文献
1
Enzymatic Logic of Ubiquitin Chain Assembly.
Front Physiol. 2019 Jul 5;10:835. doi: 10.3389/fphys.2019.00835. eCollection 2019.
2
Crystal structure and activity-based labeling reveal the mechanisms for linkage-specific substrate recognition by deubiquitinase USP9X.
Proc Natl Acad Sci U S A. 2019 Apr 9;116(15):7288-7297. doi: 10.1073/pnas.1815027116. Epub 2019 Mar 26.
3
Breaking the chains: deubiquitylating enzyme specificity begets function.
Nat Rev Mol Cell Biol. 2019 Jun;20(6):338-352. doi: 10.1038/s41580-019-0099-1.
4
Enzymatic Assembly of Ubiquitin Chains.
Methods Mol Biol. 2018;1844:73-84. doi: 10.1007/978-1-4939-8706-1_6.
5
Principles of Ubiquitin-Dependent Signaling.
Annu Rev Cell Dev Biol. 2018 Oct 6;34:137-162. doi: 10.1146/annurev-cellbio-100617-062802. Epub 2018 Aug 15.
6
ZUFSP Deubiquitylates K63-Linked Polyubiquitin Chains to Promote Genome Stability.
Mol Cell. 2018 Apr 5;70(1):165-174.e6. doi: 10.1016/j.molcel.2018.02.024. Epub 2018 Mar 22.
7
Discovery and Characterization of ZUFSP/ZUP1, a Distinct Deubiquitinase Class Important for Genome Stability.
Mol Cell. 2018 Apr 5;70(1):150-164.e6. doi: 10.1016/j.molcel.2018.02.023. Epub 2018 Mar 22.
8
Reactive-site-centric chemoproteomics identifies a distinct class of deubiquitinase enzymes.
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9
A family of unconventional deubiquitinases with modular chain specificity determinants.
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10
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Proc Natl Acad Sci U S A. 2018 Feb 13;115(7):E1401-E1408. doi: 10.1073/pnas.1716673115. Epub 2018 Jan 29.
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