糖化物水解酶限制其基质的侧链形态,以获得额外的过渡状态稳定
Jonathan C K Quirke1,2,3, David Crich1,2,3
1Department of Pharmaceutical and Biomedical Sciences, University of Georgia, 250 West Green Street, Athens, Georgia 30602, United States.
像葡萄糖酶和β-曼诺酶这样的酶稳定了反应性糖的构成,以实现高效的水解. 然而,α-galactosidases避免了这一点,以防止能量处罚,从而影响抑制剂的设计.
科学领域:
- 生物化学
- 结构生物学
- 酵素学
背景情况:
- 碳水化合物侧链构造显著影响糖化和水解活性.
- 酶活性位稳定特定的过渡状态,影响反应途径.
研究的目的:
- 通过不同的甘氨酸酶 (GHs) 结合的首选基质侧链构造进行研究.
- 了解酶如何控制基质构成,以调节水解过程中的反应性.
- 为设计新型葡萄糖酶抑制剂提供信息.
主要方法:
- 对513个与酸盐结合的GH晶体结构的分析.
- 与自由溶液和非水解蛋白结合状态的结合态的比较.
主要成果:
- 葡萄糖酶和β-曼诺酶有利于高度反应的左,左 (gg) 形状.
- α-Galactoside水溶酶更喜欢左边,转移 (gt) 形状,以避免能量处罚.
- 酶从基质结合到产品释放,而不是自由糖.
结论:
- 酶特异的基质侧链结构对于催化效率和选择性至关重要.
- 了解这些形状偏好是设计具有增强亲和力和选择性的向葡萄糖酶抑制剂的关键.
更多相关视频
08:46Regioselective O-Glycosylation of Nucleosides via the Temporary 2',3'-Diol Protection by a Boronic Ester for the Synthesis of Disaccharide Nucleosides
Published on: July 26, 2018
11:25Targeting Cysteine Thiols for in Vitro Site-specific Glycosylation of Recombinant Proteins
Published on: October 4, 2017
相关概念视频
Oligosaccharide Assembly
Multiple sugar molecules that may or may...
Hydrolysis
Hydrolysis is a chemical reaction in which the addition of water breaks down a polymer into its simpler monomer units. For example, peptides break into amino acids, carbohydrates into simple sugars, and DNA into nucleotides. Enzymes often facilitate these processes.
Hydrolysis Reverses Dehydration Synthesis
Complex carbohydrates can be broken down by breaking the bonds between individual sugar units. The reaction breaks a glycosidic bond as water is added to the compound. The...
Oral Hypoglycemic Agents: α-Glucosidase Inhibitors
Acarbose and miglitol are...
Regioselectivity and Stereochemistry of Acid-Catalyzed Hydration
Aldehydes and Ketones with Water: Hydrate Formation
The formation of hydrates is a reversible reaction. Hydrate formation is influenced by steric and electronic factors accompanying the alkyl substituents on the carbonyl group: The rate of hydrate formation increases with a decrease in the number of alkyl groups attached to the carbonyl carbon. Hence,...
Biosynthesis of Polysaccharides
