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基于 P53 的噬菌体文库筛选:锌的产量提高和一种新的寄生虫整合分析。

Phage libraries screening on P53: Yield improvement by zinc and a new parasites-integrating analysis.

机构信息

Laboratoire de Biotechnologie Moléculaire des Eucaryotes, Centre de Biotechnologie de Sfax, Université de Sfax, Sfax, Tunisia.

出版信息

PLoS One. 2024 Oct 3;19(10):e0297338. doi: 10.1371/journal.pone.0297338. eCollection 2024.

Abstract

P53 is a transcription factor that controls a variety of genes, primarily involved in cell cycle and other processes related to cell survival and death. We have isolated peptides targeting P53 (protein and domains) using the "phage display" technique. Interestingly, adding ZnCl2 at 5-10 mM in panning solutions helped to recover more plaque-forming units at least at round one of the screening. Subtractive docking analyses were designed by using a pool of common redundant peptides known as parasites. This rationale helped us differentiate between possibly specific and non-specific bindings. We found notable differences in docking characteristics between different sets of peptides either related to different targets or related to zinc-conditions. The set of zinc-related peptides shows advantageous docking profiles: sharper binding for some positions and distinct exclusive bound residues, including the relevant R248 and R273. Zinc would have modulating/helping role in the targeting of protein P53 by phage displayed peptides in addition to an enhancement action on bacterial infection.

摘要

P53 是一种转录因子,它可以控制多种基因,主要涉及细胞周期和其他与细胞存活和死亡有关的过程。我们使用“噬菌体展示”技术分离了针对 P53(蛋白质和结构域)的肽。有趣的是,在淘选溶液中添加 5-10mM 的 ZnCl2 有助于在筛选的第一轮至少回收更多的噬菌斑形成单位。通过使用一组称为寄生虫的常见冗余肽,设计了减法对接分析。这一原理帮助我们区分可能的特异性和非特异性结合。我们发现,不同的肽集之间在对接特性上存在显著差异,这些肽集要么与不同的靶标有关,要么与锌条件有关。一组与锌有关的肽显示出有利的对接特征:在某些位置的结合更尖锐,并且有独特的专属结合残基,包括相关的 R248 和 R273。噬菌体展示肽除了对细菌感染有增强作用外,锌还可能在 P53 蛋白的靶向中起调节/辅助作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b43/11449285/2fe9a071886a/pone.0297338.g001.jpg

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