通过来自Legionella pneumophila的S-adenosylhomocysteine水解酶Lpg2021进行基质识别的结构基础
Yongshan Gao1, Rao Xie2, Yanan Chen2
1Institute of Health Sciences and Technology, Institutes of Material Science and Information Technology, Anhui University, Hefei 230601, China; School of Resources and Environmental Engineering, Anhui University, Hefei 230601, China.
International journal of biological macromolecules
|May 12, 2024
概括
研究人员阐明了一个关键酶S-Adenosyl-l-homocysteine hydrolase (SAHH) 的结构,来自Legionella pneumophila. 这种结构性洞察力有助于开发针对军团士兵的新药.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 微生物学 微生物学
背景情况:
- 通过S-adenosyl methionine (SAM) 和S-adenosyl homocysteine (SAH) 水平来调节细胞甲基化,S-adenosyl-l-homocysteine hydrolase (SAHH) 对于调节细胞甲基化至关重要.
- 导致军团士兵病的细菌 - - Legionella pneumophila - - 具有独特的二维SAHH (Lpg2021),是潜在的药物标.
研究的目的:
- 确定Lpg2021功能和连接体相互作用的结构基础.
- 为设计针对Lpg2021的向抑制剂提供一个框架.
主要方法:
- 采用X射线晶体学,以解决Lpg2021在无联体和复杂状态中的结构.
- 使用异热定位热量计 (ITC) 和分子对接来分析结合相互作用.
- 进行虚拟查以确定潜在的Lpg2021抑制剂.
主要成果:
- 该研究报告了Lpg2021的晶体结构,其中包括腺因 (ADE),腺 (ADO) 和3-Deazaneplanocin A (DZNep).
- 已经阐明了基质和抑制剂对Lpg2021的详细结合机制.
- 通过虚拟查确定了Lpg2021的潜在抑制剂.
结论:
- 这项研究为SAHH进化和细菌酶结构提供了新的见解.
- 确定的结构为开发针对L. pneumophila SAHH.的特定抑制剂提供了基础.
- 针对Lpg2021是一个有前途的策略来打击军团病.
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
Ligand Binding Sites
12.8K
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
12.8K
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
Lysosomal Hydrolases
3.8K
Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
3.8K


