脂酶D超级家族的转移:一个量子力学理论研究
Nathan J DeYonker1, Charles Edwin Webster
1The Department of Chemistry, The University of Memphis , 213 Smith Chemistry Building, Memphis, Tennessee 38152-3550, United States.
Journal of the American Chemical Society
|September 7, 2013
概括
这项研究理论上研究了脂酶D (PLD) 酶的机制. 计算揭示了为什么稳定的中间体在体外而不是体内形成,解释了酶的行为.
科学领域:
- 生物化学和分子生物学
- 计算化学计算化学
- 酶学 是一种酶学.
背景情况:
- 脂酶D (PLD) 酶,以HKD动机为特征,水解酸丁胆,产生酸和胆.
- 了解催化机制和中间稳定性对于阐明PLD功能至关重要.
研究的目的:
- 从理论上研究含有HKD的脂酶D的反应机制.
- 为了合理化在体外观察到的五坐标胺中间体的持久性.
- 为了比较体外和体外的反应动态和产品形成.
主要方法:
- 使用的混合ONIOM QM:QM (DFT:PM6) 计算方法.
- 模拟了酶活性部位,包括十九种氨基酸残留物,四个水分子和基质.
- 分析了转移,水解和产品形成的热力学和动力学数据.
主要成果:
- 合理化了短暂的五坐标酸中间体在体外持续数分钟的持续时间.
- 在实验室中证明了四坐标氏丁产品的热力学优势.
- 在体内进行基质重组时确定了高激活能量,这归因于脂质双层不运动性和硬质质量.
结论:
- 氏胺中间体的稳定性在体外和体内条件之间有显著差异.
- 在体内,由于动力障碍,酶沿膜迁移比死结产品形成更受青.
- 计算建模为脂酶D超级家族酶的机械细微差别提供了关键的见解.
相关概念视频
Phosphoinositides and PIPs
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Phosphorylation
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...
Protein Kinases and Phosphatases
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...
IP3/DAG Signaling Pathway
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
Asymmetric Lipid Bilayer
Biological membranes show uneven distribution of different types of lipids in the inner and outer layers, resulting in transverse asymmetric membranes. The treatment of the erythrocyte membrane with the enzyme phospholipase confirmed the asymmetric nature of the lipid bilayer. The enzyme hydrolyzes lipids into fatty acids and hydrophilic groups. The phospholipase acts only on the outer layer of the membrane, while the inner layer remains intact. The phospholipase treatment resulted in 80%...
Synthesis of Phosphatidylcholine in the ER Membrane
The ER synthesizes lipids for building cell membranes and performing cellular functions such as energy storage and signaling. The lipid synthesis machinery embedded in the ER membrane primarily collects all reactants from the cytosol. Following synthesis, the secretory pathway and the ER contact sites distribute these lipids to other cellular organelles. Additionally, the energy-rich triacylglycerides are transported from the ER via lipid droplets.
The major components of all eukaryotic cell...
The major components of all eukaryotic cell...

