抗生素安福特里辛B是如何进入膜的,它在那里做什么?
Sebastian Janik1, Rafal Luchowski1,2, Ewa Grela1,3
1Department of Biophysics, Institute of Physics, Maria Curie-Sklodowska University, 20-031 Lublin, Poland.
The journal of physical chemistry letters
|April 26, 2024
概括
安福特里辛B的抗真菌活性取决于厄戈斯特醇. 这种抗生素形成了膜孔和集群,破坏了真菌脂质膜和功能.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 菌类学 菌类学是指菌类学.
背景情况:
- 安福特里辛B是一种广泛使用的抗真菌抗生素.
- 它对真菌膜的确切作用机制仍在争论中.
- 真菌细胞膜含有厄戈斯特醇,这是一个关键的类固醇.
研究的目的:
- 为了研究安福特里辛B在脂质膜中融入的机制.
- 分析AMPHOTERICIN B.诱导的膜的分子重组.
- 阐明膜变化与抗真菌活性之间的关系.
主要方法:
- 使用固体支的类胆单层,以埃尔戈斯特作为模型真菌膜.
- 使用原子力显微镜 (AFM) 进行高分辨率成像.
- 使用终身成像光显微镜 (LIFM) 研究分子动力学.
主要成果:
- 氨基氨酸B的内部化到膜中需要埃尔戈斯特醇的存在.
- 观察到安福特里辛B二元体的膜内集群的形成.
- 鉴定了大膜毛孔 (直径约15纳米),由抗生素诱导.
- 证明了影响膜结构和功能的同时多种作用模式.
结论:
- 埃尔戈斯特醇对于安福特素B的膜相互作用和抗真菌功效至关重要.
- 氨基氨酸B通过形成集群和孔隙来破坏真菌膜.
- 这些结构变化导致膜完整性和生理功能丧失.
相关概念视频
Facilitated Diffusion
450
The plasma membrane, a critical structure in cellular biology, houses an array of transporters, or carrier proteins, interspersed within its lipid bilayer. These proteins play a crucial role in solute transport through facilitated diffusion, a form of passive diffusion that uses transporters to move the molecules across the membrane.
In this process, substrates such as organic compounds and ions interact with a transporter on one side, triggering conformational changes in proteins that enable...
In this process, substrates such as organic compounds and ions interact with a transporter on one side, triggering conformational changes in proteins that enable...
450
Pore Transport and Ion-Pair Transport
436
Pore transport and ion-pair formation are critical mechanisms for the absorption and distribution of drugs in the body.
Pore transport, also known as convective transport, is a process where small molecules like urea, water, and sugars rapidly cross cell membranes as though there were channels or pores in the membrane. Although direct microscopic evidence is limited but the concept of pores or channels is widely accepted based on physiological evidence. Despite the lack of direct...
Pore transport, also known as convective transport, is a process where small molecules like urea, water, and sugars rapidly cross cell membranes as though there were channels or pores in the membrane. Although direct microscopic evidence is limited but the concept of pores or channels is widely accepted based on physiological evidence. Despite the lack of direct...
436
Mechanisms of Membrane-bending
2.7K
The living membranes are flexible due to their fluid mosaic nature; however, their bending into different shapes is an active process regulated by specific lipids and proteins. The membrane bending can be transient as seen in vesicles or stable for a long time as in microvilli. Cells regulate the size, location, and duration of the membrane curvature.
Membrane bending can happen due to intrinsic changes in lipid composition or extrinsic association with different proteins. The proteins involved...
Membrane bending can happen due to intrinsic changes in lipid composition or extrinsic association with different proteins. The proteins involved...
2.7K
Drug Absorption Mechanism: Passive Membrane Transport
3.8K
Passive transport is a method of drug absorption where small, lipid-soluble drugs can move across the cell membrane. This movement happens along the concentration gradient, which is a natural flow from higher to lower concentration areas. The speed at which the drug moves is directly related to its lipid–water partition coefficient. This means that the more a drug dissolves in lipids, the faster it diffuses or spreads throughout the body. It is important to note that most drugs are either...
3.8K
Mechanisms of Drug Absorption: Paracellular, Transcellular, and Vesicular Transport
517
Drugs need to permeate cell membranes to reach their target sites after administration. Orally administered drugs must transcend intestinal epithelial membrane barriers to infiltrate the systemic circulation. Drugs with a molecular weight of less than 500 Daltons diffuse through gaps between neighboring cells, called paracellular pathways.
However, most drugs use the transcellular route, traversing directly through the cell membranes via two mechanisms: passive and active transport. Passive...
However, most drugs use the transcellular route, traversing directly through the cell membranes via two mechanisms: passive and active transport. Passive...
517
Cellular Membranes and Drug Transport
502
Drugs must traverse multiple biological barriers, such as multi-layered skin, single-layered intestinal epithelium, and the plasma membrane, to reach their target sites within the body. The plasma membrane, a highly structured composite of phospholipids, carbohydrates, and proteins, is the cell's protective boundary, facilitating selective substance exchange.
Phospholipids arrange themselves into a bilayer, with hydrophilic heads oriented outward and hydrophobic tails facing inward.
Phospholipids arrange themselves into a bilayer, with hydrophilic heads oriented outward and hydrophobic tails facing inward.
502


