RNA聚合酶"切换区域"是抑制剂的目标
Jayanta Mukhopadhyay1, Kalyan Das, Sajida Ismail
1Howard Hughes Medical Institute, Rutgers University, Piscataway, NJ 08854, USA.
Cell
|October 30, 2008
概括
米克索皮罗宁抗生素通过向切换区域来抑制细菌RNA聚合酶 (RNAP),防止DNA结合. 这种机制为广泛的抗菌药物开发提供了新的途径.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 药物发现 药物发现 药物发现
背景情况:
- 细菌RNA聚合酶 (RNAP) 是抗生素的关键目标.
- 现有的RNAP抑制剂向与切换区域不同的地方.
研究的目的:
- 阐明myxopyronin (Myx) 对细菌RNAP的作用机制.
- 研究RNAP切换区域作为新型抗生素的点的潜力.
主要方法:
- 基因分析 基因分析
- 生物化学测定 生物化学测定
- 结构研究 (例如,X射线晶体学)
- 对抗生素耐药性进行分析.
主要成果:
- Myx与RNAP开关区域结合,抑制RNAP促进器DNA相互作用.
- Myx 阻止了转录启动所需的RNAP活性中心裂的开放.
- 结构相关的抗生素 (珊瑚皮罗宁) 和非相关的抗生素 (利波斯塔丁) 分享这种抑制机制.
- 麦克斯,珊瑚皮罗宁和利波沙丁没有与现有的RNAP抑制剂产生交叉耐药性.
结论:
- RNAP切换区域是抗菌剂的新目标.
- 麦克索皮罗宁和相关化合物代表了一类新的RNAP抑制剂.
- 针对转换区域提供了开发具有新型作用机制的宽谱抗生素的潜力.
相关概念视频
The Resting Membrane Potential
117.8K
Overview
117.8K
Riboswitches
8.0K
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...
8.0K
Resting Membrane Potential
18.4K
The relative difference in electrical charge, or voltage, between the inside and the outside of a cell membrane, is called the membrane potential. It is generated by differences in permeability of the membrane to various ions and the concentrations of these ions across the membrane.
The Inside of a Neuron is More Negative
The membrane potential of a cell can be measured by inserting a microelectrode into a cell and comparing the charge to a reference electrode in the extracellular fluid. The...
The Inside of a Neuron is More Negative
The membrane potential of a cell can be measured by inserting a microelectrode into a cell and comparing the charge to a reference electrode in the extracellular fluid. The...
18.4K
Drug-Receptor Interaction: Antagonist
4.9K
An antagonist is a drug that binds strongly to a receptor without activating it. An antagonist prevents other molecules, such as neurotransmitters or hormones, from binding to the receptor and triggering a cellular response. Such interaction effectively hinders the normal physiological processes mediated by the receptor, resulting in various pharmacological effects depending on the specific receptor targeted.
Antagonists can be classified as competitive or noncompetitive based on their...
Antagonists can be classified as competitive or noncompetitive based on their...
4.9K
Neuromuscular Junction And Blockade
5.9K
The site of chemical communication between a motor neuron and a muscle fiber is called the neuromuscular junction (NMJ). The end of the motor neuron at the NMJ divides into a cluster of synaptic end bulbs. The cytoplasm of these bulbs consists of synaptic vesicles enclosing acetylcholine molecules, the principal neurotransmitter released at the NMJ. The region opposite the synaptic bulb that ends in the muscle fiber is called the motor end plate, which has acetylcholine receptors. Within the...
5.9K
Nondepolarizing (Competitive) Neuromuscular Blockers: Mechanism of Action
3.6K
Nondepolarizing neuromuscular blockers induce paralysis by competitively blocking nicotinic acetylcholine receptors at the muscle end plate. Examples include pancuronium, mivacurium, vecuronium, and rocuronium. These quaternary ammonium derivatives are administered intravenously, are poorly absorbed, and are excreted via the kidneys.
Competitive antagonists prevent acetylcholine from binding to its receptor, inhibiting membrane depolarization. Without conformational changes or intrinsic...
Competitive antagonists prevent acetylcholine from binding to its receptor, inhibiting membrane depolarization. Without conformational changes or intrinsic...
3.6K


