皮科林胺杀菌剂向细胞染色体bc1复合物的相互作用机制及其结构修饰
Ying Dong1, Bo Li1, Mao-Xue Yin1
1National Key Laboratory of Green Pesticide, Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, International Joint Research Center for Intelligent Biosensor Technology and Health of Ministry of Science and Technology, Central China Normal University, Wuhan 430079, People's Republic of China.
Journal of agricultural and food chemistry
|February 12, 2024
概括
皮科林胺杀菌剂向bc1复合体的Qi位点. 这项研究揭示了它们的结合方式,并设计了新的衍生品,为开发新型杀菌剂提供了洞察力.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 农业科学 农业科学
背景情况:
- 皮科利纳米德杀菌剂在结构上与UK-2A和抗菌素A相似,已知可以结合bc1复合体的Qi位点.
- 皮科林胺杀菌剂在Qi部位的精确结合机制仍然不完全理解.
研究的目的:
- 阐明皮科林胺杀菌剂在bc1复合体的Qi位点内的详细结合方式.
- 设计和合成新的皮科利纳米德衍生物,并评估它们的杀菌活性.
- 了解尾翼基环上的替代剂的结构-活性关系.
主要方法:
- 用分子动力学 (MD) 模拟来研究抑制剂结合.
- 分子对接和分子力学通用化出生表面积 (MM/GBSA) 计算被整合.
- 进行了新型皮科利纳米德衍生物的合成和生物评估.
主要成果:
- 计算分析确定了抗菌素A和UK-2A中的替代芳香环,作为促进蛋白质结合的关键药片段.
- 化合物9g-水解对猪bc1复合体的IC50值为6.05 ± 0.24μM,与Hie201和Ash228.8形成H键.
- 化合物9c与花皮可胺相比,对黄瓜菌菌的控制能力更强,扩大了皮可胺的杀菌谱.
结论:
- 该研究提供了详细的结构和机制洞察力,了解皮科利纳米德真菌杀菌剂在Qi部位的结合.
- 这些发现为下一代位抑制剂的合理设计提供了宝贵的指导,具有增强的杀菌性质.
相关概念视频
Allosteric Proteins-ATCase
5.7K
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
5.7K
The Electron Transport Chain
16.7K
The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
16.7K
Drugs that Destabilize Microtubules
2.0K
Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
2.0K
Covalently Linked Protein Regulators
6.8K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
6.8K
Pinching-off of Coated Vesicles
3.1K
Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
3.1K
Drug Metabolism: Phase I Reactions
3.3K
A phase I reaction is a biochemical process that introduces a functionally reactive polar group to a substance. This transformation predominantly occurs in the liver, facilitated by the cytochrome P450 system of hemoproteins situated in the lipophilic endoplasmic reticulum of cells. The metabolite generated through this process can have varying polarities. If it is sufficiently polar, it can be easily excreted in the urine due to its water compatibility. However, if the metabolite is nonpolar,...
3.3K


