体结合 乙烯酸酸酶的混合性,解毒血清酸酶的结构分析
Anna J Kiss-Szemán1, Luca Takács1, Imre Jákli2
1Laboratory of Structural Chemistry and Biology, Institute of Chemistry, Eötvös Loránd University, Budapest, Hungary.
Protein science : a publication of the Protein Society
|October 11, 2025
概括
哺乳动物酸化酶 (APEH) 由于独特的烯残留物,表现出广泛的基质特异性. 这种结构洞察力解释了它在蛋白质代谢和排毒中的多功能作用.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 酶学 是一种酶学.
背景情况:
- 乙酸酸酶 (APEH),也称为乙胺酸酸酶 (AAP),是一种酸酸酶,参与蛋白质代谢和排毒.
- 其杂乱的基质特异性尚未得到充分理解,这阻碍了对其生理作用的充分理解.
研究的目的:
- 阐明哺乳动物APEH的广泛基质特异性的结构基础.
- 研究APEH与各种抑制剂和基质的相互作用,包括甲基 (CMK) 抑制剂和有机酸盐 (OP) 农药.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来确定哺乳动物APEH的结构.
- 分析了APEH与CMK抑制剂,二伏 (一种OP农药) 和硫-化物复合物的复合物.
主要成果:
- 冷-EM结构揭示了哺乳动物APEH的酶域内的独特的"断链"Pro残留物.
- 这种普罗林残留物诱导了形状变化,使活性部位放松,成为一个更宽和多功能的水解中心.
- 这种结构适应解释了APEH的广泛特异性,使其与其他APEH和氨酸α/β酸酶区别开来.
结论:
- 识别的结构特征,一种独特的烯残留物,是APEH乱交特异性及其在蛋白质代谢和排毒中的双重作用的关键.
- 了解这些结构基质相互作用,可以了解APEH的生理意义,包括其作为OP暴露生物标志物的潜力以及与认知影响的联系.
更多相关视频
08:49Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
Published on: June 20, 2025
1.1K
11:27X-Ray Crystallography to Study the Oligomeric State Transition of the Thermotoga maritima M42 Aminopeptidase TmPep1050
Published on: May 13, 2020
4.3K
相关概念视频
00:49Ligand Binding and Linkage
5.5K
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...
5.5K
02:40Ligand Binding Sites
14.9K
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...
14.9K
01:19Allosteric Proteins-ATCase
6.5K
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...
6.5K
01:22Lysosomal Hydrolases
4.4K
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,...
4.4K