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核仁人硒蛋白H的半合成

The semisynthesis of nucleolar human selenoprotein H.

作者信息

Dardashti Rebecca Notis, Laps Shay, Gichtin Jacob S, Metanis Norman

机构信息

The Institute of Chemistry, The Hebrew University of Jerusalem Edmond J. Safra Campus Givat Ram Jerusalem 9190401 Israel.

Casali Center for Applied Chemistry, The Hebrew University of Jerusalem Edmond J. Safra Campus Givat Ram Jerusalem 9190401 Israel.

出版信息

Chem Sci. 2023 Oct 24;14(44):12723-12729. doi: 10.1039/d3sc03059h. eCollection 2023 Nov 15.

Abstract

The human selenoprotein H is the only selenocysteine-containing protein that is located in the cell's nucleolus. studies have suggested that it plays some role in DNA binding, consumption of reactive oxygen species, and may serve as a safeguard against cancers. However, the protein has never been isolated and, as a result, not yet fully characterized. Here, we used a semi-synthetic approach to obtain the full selenoprotein H with a S43T mutation. Using biolayer interferometry, we also show that the Cys-containing mutant of selenoprotein H is capable of binding DNA with sub-micromolar affinity. Employing state-of-the-art expressed protein ligation (EPL), our devised semi-synthetic approach can be utilized for the production of numerous, hard-to-obtain proteins of biological and therapeutic relevance.

摘要

人类硒蛋白H是唯一一种位于细胞核仁中的含硒代半胱氨酸的蛋白质。研究表明,它在DNA结合、活性氧的消耗中发挥一定作用,可能具有抗癌作用。然而,该蛋白质从未被分离出来,因此尚未得到充分表征。在这里,我们使用半合成方法获得了具有S43T突变的完整硒蛋白H。使用生物层干涉术,我们还表明,含半胱氨酸的硒蛋白H突变体能够以亚微摩尔亲和力结合DNA。采用最先进的表达蛋白连接(EPL)技术,我们设计的半合成方法可用于生产许多具有生物学和治疗相关性的难以获得的蛋白质。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d9b/10646972/70afa40843cc/d3sc03059h-f1.jpg

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