在PNP中酸盐结合改变了过渡状态的模拟亲和力和子单位合作性
Yacoba V T Minnow1, Vern L Schramm1, Steven C Almo1
1Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, United States.
Biochemistry
|October 9, 2023
概括
纯核酸酸化酶 (PNPs) 是重要的酶. 了解它们的酸盐结合部位解释了酶功能和人类遗传疾病.
科学领域:
- 生物化学 生物化学
- 酶学 是一种酶学.
- 分子生物学分子生物学
背景情况:
- 纯氨酸核酸酸化酶 (PNPs) 催化了纯氨酸代谢中的重要反应.
- 在PNP中,酸盐离子 (HPO42-) 作为其活性位点内的核友.
- 酸盐结合部位在PNP活动和调节中的确切作用尚未完全理解.
研究的目的:
- 研究纯核酸酶 (PNPs) 中的酸盐 (HPO42-) 结合部位的结构和功能意义.
- 阐明酸盐结合部位的变化如何影响酶活性,亚单元合作性和抑制剂结合.
- 为了将发现与人类PNP缺陷综合征相关联.
主要方法:
- 在HPO42-结合部位的位点定向突变发生.
- 合作有约束力的研究.
- 热力学分析.热力学分析.
- 结构分析. 结构分析.
- 对过渡状态模拟抑制剂结合的评估.
主要成果:
- 在HPO42-结合部位的突变使PNP变得不活跃.
- 改变的酸盐结合显著影响了子单位的合作性.
- 抑制剂和酸盐位点之间的合作相互作用对于最佳的过渡状态模拟抑制至关重要.
- 改性酸盐结合解释了致命的PNP缺陷综合征.
结论:
- HPO42-结合部位对PNP催化活性和整体酶功能至关重要.
- 小单位的合作性与酸盐结合部位密切相关.
- 了解酸盐结合是开发有效过渡状态模拟抑制剂的关键.
- 在PNP中功能障碍的酸盐结合直接与人类遗传疾病有关.
相关概念视频
Cooperative Allosteric Transitions
7.9K
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
7.9K
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
Cooperative Binding of Transcription Regulators
6.5K
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
6.5K
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
Protein Kinases and Phosphatases
13.2K
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
13.2K
Phosphorylation
50.4K
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
50.4K


