蒙面烯可以实现双位点选择性蛋白质交叉链接
Ziran Jiang1, Aochiu Chen1, Jeffrey Chen1
1Department of Chemistry and Biochemistry, University of California San Diego La Jolla CA 92093-0358 USA mburkart@ucsd.edu.
Chemical science
|October 13, 2023
概括
研究人员修改了真菌代谢物cerulenin,以创建新的光探针. 这些探测器使得脂肪酸和多基酸合成酶的研究成为可能,为了解这些重要的生物合成途径提供了新的工具.
科学领域:
- 自然产品化学 自然产品化学
- 化学生物学 化学生物学
- 酶学 是一种酶学.
背景情况:
- 蛋白质反应性天然产品,如烯,是有价值的治疗候选者,因为它们与蛋白质活性部位的选择性反应性.
- 脂肪酸合成酶 (FAS) 和多基合成酶 (PKS) 是生物合成中的关键酶,但研究它们的活性和结构仍然具有挑战性.
研究的目的:
- 开发基于烯的新型化学探针,用于研究FAS和PKS酶.
- 为了适应这些类酶的光标记和交叉链接,Cerulenin的反应性.
- 创建新的蒙面交联探测器,以进行先进的活动和生物合成途径的结构调查.
主要方法:
- 合成调节氨酸的功能部分以改变其反应性.
- 基于机理的研究,研究烯独特的化学性质.
- 开发光标签和交叉连接策略,使用改性烯.
- 设计和合成锡基水素和锡基胺蒙面交叉连接探针.
主要成果:
- 成功合成修改烯产生的探针与定制的反应性.
- 已证明改性烯对脂肪酸和代型I型多基酸合成酶的光标记和交联的实用性.
- 介绍了两种新型的蒙面交叉连接探头类别,扩大了生物化学研究的工具包.
结论:
- 改性烯酸衍生物作为有效的工具来研究FAS和PKS酶.
- 开发的探测器有助于光标签,交叉连接和这些关键生物合成途径的结构研究.
- 新的蒙面交联探针为探索酶活性和机制提供了增强的能力.
更多相关视频
10:50Isolation of Labile Multi-protein Complexes by in vivo Controlled Cellular Cross-Linking and Immuno-magnetic Affinity Chromatography
Published on: March 9, 2010
17.4K
10:12Author Spotlight: Quantitative Detection of DNA Protein Crosslinks and Their Post-Translational Modifications
Published on: April 21, 2023
2.8K
相关概念视频
Ligand Binding and Linkage
4.8K
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
4.8K
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
Catenins
2.3K
Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...
2.3K
Assembly of Signaling Complexes
5.8K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
5.8K
Tension Response at Adherens Junctions
2.7K
The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
2.7K
Allosteric Proteins-ATCase
5.8K
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...
5.8K
