酸酸脱化中的特异性决定因素:原型酸聚酸5-酸酶的晶体结构
Y Tsujishita1, S Guo, L E Stolz
1Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, , Bethesda, MD 20892, USA.
Cell
|May 12, 2001
概括
内醇多酸5-酸酶对细胞功能至关重要,并与洛伊综合征有关. 结构分析揭示了它们的酶机制和基质识别,有助于了解疾病和酶特异性.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 伊诺西聚酸5-酶调节重要的细胞过程,如膜贩运和信号传递.
- 这些酶的功能障碍与人类疾病有关,特别是洛伊综合征.
研究的目的:
- 阐明伊诺西多酸盐5-酸酶活性的结构基础.
- 了解基质识别和脱化位点选择性的基础分子机制.
- 为了确定酶基质相互作用的决定因素.
主要方法:
- 进行X射线晶体学以确定SPsynaptojanin的5酸酶域的3D结构.
- 酶-连接体复合物的生物化学分析 (Ca2+和伊诺西 (1,4) - 双酸盐).
- 位点定向的突变发生来探测基质的特异性.
主要成果:
- 1.8 Å分辨率结构显示了一个类似于Mg2+依赖核酶的折叠,具有催化His-Asp对.
- 确定了因诺西聚酸盐结合的特定循环.
- 伊诺西 (1,4) - 双酸盐的方向阐明了酶的脱化位点选择性.
结论:
- 已确定的结构提供了关于伊诺西聚酸5-酸酶的催化机制的见解.
- 了解基质识别机制可以为在疾病背景下向酶的策略提供信息.
- 突变性研究确定了控制基质特异性的关键残留物.
更多相关视频
相关概念视频
Phosphorylation
44.8K
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...
44.8K
Protein Kinases and Phosphatases
12.1K
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...
12.1K
Phosphoinositides and PIPs
7.7K
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...
7.7K
Mechanism of Filopodia Formation
2.5K
Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
2.5K
IP3/DAG Signaling Pathway
12.5K
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...
12.5K


