抑制细菌核糖体组装：一个合适的药物靶点？
Inhibition of bacterial ribosome assembly: a suitable drug target?
作者信息
Maguire Bruce A
机构信息
Department of Exploratory Medicinal Sciences, Pfizer Global Research and Development, MS 8118W-106, Groton Laboratories, Groton, CT 06340, USA.
出版信息
Microbiol Mol Biol Rev. 2009 Mar;73(1):22-35. doi: 10.1128/MMBR.00030-08.
Abstract
The assembly of bacterial ribosomes is viewed with increasing interest as a potential target for new antibiotics. The in vivo synthesis and assembly of ribosomes are briefly reviewed here, highlighting the many ways in which assembly can be perturbed. The process is compared with the model in vitro process from which much of our knowledge is derived. The coordinate synthesis of the ribosomal components is essential for their ordered and efficient assembly; antibiotics interfere with this coordination and therefore affect assembly. It has also been claimed that the binding of antibiotics to nascent ribosomes prevents their assembly. These two contrasting models of antibiotic action are compared and evaluated. Finally, the suitability and tractability of assembly as a drug target are assessed.
摘要
细菌核糖体的组装作为新型抗生素的潜在靶点正日益受到关注。本文简要回顾了核糖体在体内的合成与组装过程，着重强调了组装过程可能受到干扰的多种方式。将该过程与我们获取大量知识所依据的体外模型过程进行了比较。核糖体组分的协同合成对于其有序且高效的组装至关重要；抗生素会干扰这种协同作用，从而影响组装。也有人认为抗生素与新生核糖体的结合会阻止其组装。对这两种截然不同的抗生素作用模型进行了比较和评估。最后，评估了组装作为药物靶点的适用性和可操作性。
相似文献
1
Inhibition of bacterial ribosome assembly: a suitable drug target?抑制细菌核糖体组装：一个合适的药物靶点？
Microbiol Mol Biol Rev. 2009 Mar;73(1):22-35. doi: 10.1128/MMBR.00030-08.
2
Context-Specific Action of Ribosomal Antibiotics.核糖体抗生素的语境特异性作用。
Annu Rev Microbiol. 2018 Sep 8;72:185-207. doi: 10.1146/annurev-micro-090817-062329. Epub 2018 Jun 15.
3
Antimicrobial agents targeting the ribosome: the issue of selectivity and toxicity - lessons to be learned.靶向核糖体的抗菌剂：选择性和毒性问题——可吸取的教训
Cell Mol Life Sci. 2007 Apr;64(7-8):791-5. doi: 10.1007/s00018-007-6431-5.
4
Bacterial ribosomal subunit assembly is an antibiotic target.细菌核糖体亚基组装是一个抗生素作用靶点。
Curr Top Med Chem. 2003;3(9):929-47. doi: 10.2174/1568026033452186.
5
The bacterial ribosome as a target for antibiotics.作为抗生素作用靶点的细菌核糖体。
Nat Rev Microbiol. 2005 Nov;3(11):870-81. doi: 10.1038/nrmicro1265.
6
Erythromycin- and chloramphenicol-induced ribosomal assembly defects are secondary effects of protein synthesis inhibition.红霉素和氯霉素诱导的核糖体组装缺陷是蛋白质合成抑制的次要效应。
Antimicrob Agents Chemother. 2009 Feb;53(2):563-71. doi: 10.1128/AAC.00870-08. Epub 2008 Nov 24.
7
The other target for ribosomal antibiotics: inhibition of bacterial ribosomal subunit formation.核糖体抗生素的另一个作用靶点：抑制细菌核糖体亚基的形成。
Infect Disord Drug Targets. 2006 Dec;6(4):377-90. doi: 10.2174/187152606779025842.
8
In vitro ribosome synthesis and evolution through ribosome display.通过核糖体展示进行体外核糖体合成和进化。
Nat Commun. 2020 Feb 28;11(1):1108. doi: 10.1038/s41467-020-14705-2.
9
Enhanced SnapShot: Antibiotic inhibition of protein synthesis II.增强快照：抗生素对蛋白质合成的抑制作用II。
Cell. 2009 Oct 2;139(1):212-212.e1. doi: 10.1016/j.cell.2009.08.009.
10
Blast from the Past: Reassessing Forgotten Translation Inhibitors, Antibiotic Selectivity, and Resistance Mechanisms to Aid Drug Development.从过去中汲取灵感：重新评估被遗忘的抗生素翻译抑制剂、抗生素选择性和耐药机制，以帮助药物研发。
Mol Cell. 2016 Jan 7;61(1):3-14. doi: 10.1016/j.molcel.2015.10.019. Epub 2015 Nov 12.
引用本文的文献
1
Comparison of transcriptomic profiles between intracellular and extracellular Bartonella henselae.亨氏巴尔通体细胞内和细胞外转录组图谱的比较。
Commun Biol. 2025 Jan 29;8(1):143. doi: 10.1038/s42003-025-07535-9.
2
The proline-rich antimicrobial peptide Api137 disrupts large ribosomal subunit assembly and induces misfolding.富含脯氨酸的抗菌肽Api137破坏大核糖体亚基组装并诱导错误折叠。
Nat Commun. 2025 Jan 10;16(1):567. doi: 10.1038/s41467-025-55836-8.
3
Uncovering the transcriptome-wide RNA modifications in .揭示. 中的转录组范围的 RNA 修饰。
Microb Genom. 2024 Nov;10(11). doi: 10.1099/mgen.0.001327.
4
Chloramphenicol Interferes with 50S Ribosomal Subunit Maturation via Direct and Indirect Mechanisms.氯霉素通过直接和间接机制干扰 50S 核糖体亚基成熟。
Biomolecules. 2024 Sep 27;14(10):1225. doi: 10.3390/biom14101225.
5
Computational analysis of RNA methyltransferase Rv3366 as a potential drug target for combating drug-resistant .RNA甲基转移酶Rv3366作为抗耐药性潜在药物靶点的计算分析
Front Mol Biosci. 2024 Jan 11;10:1348337. doi: 10.3389/fmolb.2023.1348337. eCollection 2023.
6
Potential therapeutic targets for combating .对抗……的潜在治疗靶点
3 Biotech. 2023 Jan;13(1):9. doi: 10.1007/s13205-022-03423-9. Epub 2022 Dec 15.
7
fingeRNAt-A novel tool for high-throughput analysis of nucleic acid-ligand interactions.fingERNAt—一种用于高通量分析核酸-配体相互作用的新工具。
PLoS Comput Biol. 2022 Jun 2;18(6):e1009783. doi: 10.1371/journal.pcbi.1009783. eCollection 2022 Jun.
8
Discovery of a novel small molecular peptide that disrupts helix 34 of bacterial ribosomal RNA.发现一种破坏细菌核糖体RNA螺旋34的新型小分子肽。
RSC Adv. 2019 Dec 4;9(69):40268-40276. doi: 10.1039/c9ra07812f. eCollection 2019 Dec 3.
9
Sub-Inhibitory Concentrations of Oxacillin, but Not Clindamycin, Linezolid, or Tigecycline, Decrease Staphylococcal Phenol-Soluble Modulin Expression in Community-Acquired Methicillin-Resistant Staphylococcus aureus.亚抑菌浓度的苯唑西林，但克林霉素、利奈唑胺或替加环素，可降低社区获得性耐甲氧西林金黄色葡萄球菌的葡萄球菌酚可溶性调节素表达。
Microbiol Spectr. 2022 Feb 23;10(1):e0080821. doi: 10.1128/spectrum.00808-21. Epub 2022 Jan 19.
10
Uncovering a delicate balance between endonuclease RNase III and ribosomal protein S15 in E. coli ribosome assembly.揭示大肠杆菌核糖体组装中内切核酸酶 RNase III 和核糖体蛋白 S15 之间的微妙平衡。
Biochimie. 2021 Dec;191:104-117. doi: 10.1016/j.biochi.2021.09.003. Epub 2021 Sep 8.
本文引用的文献
1
Erythromycin- and chloramphenicol-induced ribosomal assembly defects are secondary effects of protein synthesis inhibition.红霉素和氯霉素诱导的核糖体组装缺陷是蛋白质合成抑制的次要效应。
Antimicrob Agents Chemother. 2009 Feb;53(2):563-71. doi: 10.1128/AAC.00870-08. Epub 2008 Nov 24.
2
Inhibition of chaperone-dependent bacterial ribosome biogenesis.伴侣蛋白依赖性细菌核糖体生物合成的抑制作用。
Methods Mol Med. 2008;142:75-85. doi: 10.1007/978-1-59745-246-5_7.
3
Targeting RNA with small molecules.用小分子靶向RNA。
Chem Rev. 2008 Apr;108(4):1171-224. doi: 10.1021/cr0681546. Epub 2008 Mar 25.
4
Characteristics of a 50S ribosomal subunit precursor particle as a substrate for ermE methyltransferase activity and erythromycin binding in Staphylococcus aureus.50S核糖体亚基前体颗粒作为金黄色葡萄球菌中ermE甲基转移酶活性和红霉素结合底物的特性
RNA Biol. 2007 Nov;4(3):147-53. doi: 10.4161/rna.4.3.5346. Epub 2007 Nov 25.
5
Characterization of a 30S ribosomal subunit assembly intermediate found in Escherichia coli cells growing with neomycin or paromomycin.在新霉素或巴龙霉素存在下生长的大肠杆菌细胞中发现的30S核糖体亚基组装中间体的表征。
Arch Microbiol. 2008 May;189(5):441-9. doi: 10.1007/s00203-007-0334-6. Epub 2007 Dec 5.
6
Structural aspects of RbfA action during small ribosomal subunit assembly.小核糖体亚基组装过程中RbfA作用的结构方面
Mol Cell. 2007 Nov 9;28(3):434-45. doi: 10.1016/j.molcel.2007.08.026.
7
Ribosome biogenesis and the translation process in Escherichia coli.大肠杆菌中的核糖体生物合成与翻译过程。
Microbiol Mol Biol Rev. 2007 Sep;71(3):477-94. doi: 10.1128/MMBR.00013-07.
8
A steric block in translation caused by the antibiotic spectinomycin.抗生素壮观霉素引起的翻译中的空间位阻。
ACS Chem Biol. 2007 Aug 17;2(8):545-552. doi: 10.1021/cb700100n. Epub 2007 Aug 10.
9
Structural basis for aminoglycoside inhibition of bacterial ribosome recycling.氨基糖苷类药物抑制细菌核糖体循环的结构基础。
Nat Struct Mol Biol. 2007 Aug;14(8):727-32. doi: 10.1038/nsmb1271. Epub 2007 Jul 29.
10
The weird and wonderful world of bacterial ribosome regulation.细菌核糖体调控的奇妙世界。
Crit Rev Biochem Mol Biol. 2007 May-Jun;42(3):187-219. doi: 10.1080/10409230701360843.
Zotero 插件