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结构与功能视角下的 colicin:药物研发的新范例。

Structural and functional insights into colicin: a new paradigm in drug discovery.

机构信息

Department of Microbiology, Sister Nivedita University, Kolkata, 700156, India.

出版信息

Arch Microbiol. 2021 Dec 20;204(1):37. doi: 10.1007/s00203-021-02689-6.

DOI:10.1007/s00203-021-02689-6
PMID:34928429
Abstract

Colicins are agents of allelopathic interactions produced by certain enterobacteria which give them a competitive advantage in the environment. These protein molecules are mostly encoded by plasmids. The colicin operon consists of the activity, immunity and the lysis genes. The activity protein is responsible for the killing activity, the immunity protein protects the producer cell from the lethal action of colicin and the lysis protein facilitates its release. Colicins are primarily composed of three domains, namely the receptor-binding domain, the translocation domain and the cytotoxic domain. The protein molecule binds to its cognate receptor on the target cell via the receptor-binding domain and undergoes translocation into the cell either via the Tol system or the Ton system. After gaining entry into the target cell, there are various mechanisms by which colicins exert their lethality. These comprise DNase activity, RNase activity and pore formation in the target cell membrane or peptidoglycan synthesis inhibition. This review gives a detailed insight into the structural and functional aspect of colicins and their mode of action. This knowledge is of immense significance because colicins are being considered as very useful alternatives to conventional antibiotics in the treatment of multidrug-resistant infections. Besides, they also have a negligible harmful impact on the commensals. Thus, before tapping their therapeutic potential, it is imperative to know their structure and mechanism of action in detail.

摘要

肠毒素是某些肠细菌产生的化感相互作用的制剂,使它们在环境中具有竞争优势。这些蛋白质分子主要由质粒编码。肠毒素操纵子由活性、免疫和溶素基因组成。活性蛋白负责杀伤活性,免疫蛋白保护产生细胞免受肠毒素的致死作用,而溶素蛋白促进其释放。肠毒素主要由三个结构域组成,即受体结合结构域、转运结构域和细胞毒性结构域。蛋白质分子通过受体结合结构域与靶细胞上的同源受体结合,并通过 Tol 系统或 Ton 系统进入细胞进行转运。进入靶细胞后,肠毒素通过多种机制发挥其致死作用。这些机制包括在靶细胞膜或肽聚糖合成抑制中发挥 DNA 酶、RNA 酶活性和形成孔。本综述详细介绍了肠毒素的结构和功能及其作用模式。这方面的知识非常重要,因为肠毒素被认为是治疗多药耐药感染的非常有用的抗生素替代品。此外,它们对共生菌的危害也可以忽略不计。因此,在挖掘它们的治疗潜力之前,详细了解它们的结构和作用机制是至关重要的。

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Structural and functional insights into colicin: a new paradigm in drug discovery.结构与功能视角下的 colicin:药物研发的新范例。
Arch Microbiol. 2021 Dec 20;204(1):37. doi: 10.1007/s00203-021-02689-6.
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[Structural and functional organization of the colicin operon in the ColD-CA23 plasmid].[ColD-CA23质粒中大肠杆菌素操纵子的结构与功能组织]
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Immunity protein release from a cell-bound nuclease colicin complex requires global conformational rearrangement.免疫蛋白从细胞结合核酸酶 colicin 复合物中的释放需要全局构象重排。
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Evaluation of antibacterial activity of enterocin A-colicin E1 fusion peptide.肠球菌素A-大肠杆菌素E1融合肽的抗菌活性评估
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Extracellular loops of BtuB facilitate transport of vitamin B12 through the outer membrane of E. coli.
通过核酸支架提高色氨酸合成酶的活性。
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Colicin E2 expression in Escherichia coli biofilms: Induction and regulation revisited.大肠杆菌生物膜中大肠杆菌素E2的表达:对诱导和调控的重新审视
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Impact of microcin J25 on the porcine microbiome in a continuous culture model.微小菌素J25对连续培养模型中猪微生物群的影响。
Front Microbiol. 2022 Aug 3;13:930392. doi: 10.3389/fmicb.2022.930392. eCollection 2022.
6
Characterization of ColE1 Production for Robust Plate Dual-Selection in .用于. 板双选择稳健性的 ColE1 生产的表征。
ACS Synth Biol. 2022 Jun 17;11(6):2009-2014. doi: 10.1021/acssynbio.2c00061. Epub 2022 Jun 6.
BtuB 的细胞外环有助于维生素 B12 通过大肠杆菌的外膜运输。
PLoS Comput Biol. 2020 Jul 1;16(7):e1008024. doi: 10.1371/journal.pcbi.1008024. eCollection 2020 Jul.
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Colicin Z, a structurally and functionally novel colicin type that selectively kills enteroinvasive Escherichia coli and Shigella strains.志贺样大肠菌素 Z,一种结构和功能新颖的大肠菌素,可选择性杀伤侵袭性大肠埃希菌和志贺菌。
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