在UDP-glucuronic acid 4-epimerase催化剂中的结构预组织和形状采样的相互作用
Christian Rapp1, Annika Borg1, Bernd Nidetzky2,3
1Institute of Biotechnology and Biochemical Engineering, Graz University of Technology, NAWI Graz, 8010, Graz, Austria.
Nature communications
|May 8, 2024
概括
酶催化依赖于蛋白质运动. 这项研究表明,特定的蛋白质构造对于C-H激活至关重要,需要有限的灵活性才能有效地发挥酶功能.
科学领域:
- 生物化学 生物化学
- 酶学 是一种酶学.
- 蛋白质动力学 蛋白质动力学
背景情况:
- 酶催化与蛋白质构成变化密切相关.
- 了解酶反应的能量格局,特别是C-H激活,仍然是一个挑战.
研究的目的:
- 为了提供NAD依赖的UDP-葡萄糖酸C4表酶中C-H激活的能量描述.
- 阐明到达过渡状态类反应形态 (TSRC) 的热力学要求.
主要方法:
- 温度动力学研究.
- 同位素效应测量. 同位素效应测量.
- 对影响静电基本状态预组织的酶变体的分析.
主要成果:
- 从地面状态 (GS) 过渡到TSRC涉及大量的热吸收和损失.
- 观察到负激活热容量,这表明需要限制运动.
- 活动地点的相互作用对于精确的TSRC采样和转移至关重要.
结论:
- 对于C-H激活,已经确定了酶活性部位的刚性.
- 为了使酶的自然表皮酶功能,需要符合性灵活性.
- 捕捉了与TSRC采样相关的热力学效应.
相关概念视频
Cooperative Allosteric Transitions
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...
Protein Folding Quality Check in the RER
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
Cooperative Allosteric Transitions
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...
Cooperative Allosteric Transitions
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...
Drug Metabolism: Phase II Reactions
Phase II reactions are essential for the detoxification and elimination of drugs from the body. These reactions involve the conjugation of parent drugs or their phase I metabolites with endogenous molecules, resulting in more hydrophilic drug conjugates. The primary conjugation reactions in this phase are sulfation and glucuronidation. Both sulfation and glucuronidation typically produce biologically inactive metabolites. However, in some cases involving prodrugs, active metabolites may be...
Phase II Reactions: Glucuronidation
Glucuronidation, a pivotal phase II biotransformation process, involves the coupling of glucuronic acid to a drug or xenobiotic. Given its widespread occurrence and critical role in drug metabolism, it's considered the most crucial phase II reaction. It enhances the water solubility of substances, aiding their expulsion from the body. The driving force behind these reactions is a group of enzymes known as UDP-glucuronosyltransferases (UGTs). UGTs facilitate the transfer of a glucuronic acid...


