利芬素抑制细菌RNA聚合酶的结构机制
E A Campbell1, N Korzheva, A Mustaev
1The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Cell
|April 6, 2001
概括
利芬素通过在DNA/RNA通道内结合来抑制细菌RNA聚合酶. 这种结合阻断了RNA延长,解释了它作为抗结核抗生素的有效性.
科学领域:
- 微生物学 微生物学
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- 里芬素 (Rif) 是一种强大的抗生素,对结核病治疗至关重要.
- 它通过抑制细菌RNA聚合酶 (RNAP) 起作用,这是转录的关键酶.
研究的目的:
- 阐明里芬素抑制细菌RNA聚合酶的结构基础.
- 了解里芬素在分子层面影响RNAP功能的机制.
主要方法:
- 确定了Thermus aquaticus核心RNAP与里芬素复合的晶体结构.
- 利用生物化学分析来补充结构性发现.
主要成果:
- 晶体结构揭示了里芬辛在RNAPβ子单元中的一个口袋中结合.
- 结合部位位于DNA/RNA通道的深处,远离活性部位.
- 证明,利芬素结合阻碍了在2-3个核酸处的RNA延长.
结论:
- 利芬素通过物理阻碍延长的RNA来抑制细菌RNAP.
- 结构和生化数据为利芬素的抗生素作用提供了明确的机制.
相关概念视频
Types of RNA
Overview
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
Transcription Attenuation in Prokaryotes
Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure. Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
Riboswitches
Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
Types of RNA
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in regulating gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA Performs Diverse...
RNA Performs Diverse...
Transcriptional Regulation: Riboswitches
Riboswitches are RNA elements that regulate gene expression by altering their secondary structures in response to specific effector molecules. These elements, located in the leader regions of certain mRNAs, act as transcriptional regulators by toggling between alternative conformations to control downstream gene expression. Riboswitch-mediated regulation is a precise mechanism for modulating biosynthetic pathways, as exemplified by the riboflavin biosynthesis pathway in Bacillus...
Inhibitors of Bacterial Protein Synthesis
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...


