抗生素与eubacteria中的基转移酶中心相互作用的结构基础
F Schlünzen1, R Zarivach, J Harms
1Max-Planck-Research, Unit for Ribosomal Structure, Notkestrasse 85, 22603 Hamburg, Germany.
Nature
|October 26, 2001
概括
抗生素在基转移酶腔内与核糖体RNA结合,而不是蛋白质. 这种对抗生素与核糖体相互作用的结构理解有助于开发新药.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 微生物学 微生物学
背景情况:
- 核糖体对于蛋白质合成至关重要,是抗生素的主要点.
- 了解抗生素结合部位对于阐明药物机制和核糖体功能至关重要.
研究的目的:
- 为了确定与临床相关抗生素复合的50S核糖体亚单元的高分辨率X射线结构.
- 阐明抗生素与核糖体相互作用的结构基础.
主要方法:
- 使用高分辨率的X射线晶体学来确定结构.
- 这项研究的重点是Deinococcus radiodurans的50S核糖体亚单元.
- 分析了含有氨基醇,克林达米辛,红红素,清红素和红素的复合物.
主要成果:
- 抗生素的结合部位仅由基转移酶腔内的23S核糖体RNA段组成.
- 没有观察到抗生素和核糖体蛋白之间的相互作用.
- 假定离子被发现对某些抗生素的结合很重要.
结论:
- 抗生素与核糖体的结合主要由核糖体RNA介导,而不是蛋白质.
- 这种详细的结构分析为合理的抗生素药物设计提供了基础.
- 这些发现增强了我们对抗生素作用和核糖体功能的理解.
相关概念视频
Translation in Prokaryotes
2.8K
Prokaryote translation is a complex, highly coordinated process that converts genetic information from mRNA into functional proteins. It involves three stages: initiation, elongation, and termination, each facilitated by specific molecular components.Initiation of TranslationThe process begins with the assembly of the ribosomal subunits and initiation factors on the mRNA. In bacteria, the 30S ribosomal subunit recognizes the Shine-Dalgarno sequence in the mRNA, a conserved region upstream of...
2.8K
Coordination of Gene Expression Processes in Bacteria
1.1K
The DNA replication, transcription, and translation processes are intricately coupled in bacteria, allowing efficient gene expression and rapid protein synthesis. While this physical and functional coordination is advantageous, it introduces challenges that bacteria overcome through specific regulatory mechanisms.Coupling of Replication, Transcription, and TranslationThe coupling of replication, transcription, and translation is a hallmark of bacterial gene expression. As the replisome unwinds...
1.1K
Development of Antibiotic Resistance
2.0K
Antibiotic resistance is a major public health concern that arises when bacteria evolve mechanisms to withstand the effects of antibiotic treatments. This resistance can be intrinsic, acquired through genetic mutations, or transferred between bacteria via horizontal gene transfer. The development of antibiotic resistance poses significant challenges in treating bacterial infections and necessitates ongoing research to develop new therapeutic strategies.Intrinsic resistance occurs when bacterial...
2.0K
Mechanism of Antibiotic Resistance in MRSA
215
Antibiotic resistance in bacteria arises when microorganisms evolve the ability to withstand drugs designed to kill them or inhibit their growth, rendering once-effective treatments useless. This phenomenon, driven by genetic change and selection under antibiotic exposure, poses a profound threat to modern medicine. Mechanisms include drug-inactivating enzymes (e.g., β-lactamases), efflux pumps that eject antibiotics, mutations altering antibiotic targets, decreased drug uptake, and...
215
Inhibitors of Gram-positive Cell Wall Synthesis
181
Bacterial cell walls are typically rigid structures composed mainly of peptidoglycan, a mesh-like polymer that provides mechanical strength and maintains cell shape. The synthesis of peptidoglycan is a crucial process in bacterial growth and serves as a primary target for many antibiotics.Mechanism of Action of Beta-Lactam AntibioticsBeta-lactam antibiotics, such as penicillin, inhibit peptidoglycan synthesis in actively growing cells. These antibiotics share a characteristic four-membered...
181
Inhibitors of Bacterial Protein Synthesis
102
Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...
102


