在前列腺酸酸酶中形成氏丁中间体的DFT研究
Satyan Sharma1, Arvi Rauk, André H Juffer
1Biocenter Oulu and the Department of Biochemistry, University of Oulu, Oulu, Finland.
Journal of the American Chemical Society
|July 9, 2008
概括
这项研究详细介绍了前列腺酸酸酶 (PAP) 脱酸化的第一步. 量子化学揭示了histidine (His12) 作为一个核爱者,由阿尔金因稳定,Asp258有可能捐赠质子.
科学领域:
- 生物化学 生物化学
- 酶学 是一种酶学.
- 计算化学计算化学
背景情况:
- 胺酸酶利用一个保存的RHGXRXP动机与催化胺.
- 前列腺酸酸酶 (PAP) 在两步机制中去化.
- 最初的步骤涉及将酸盐转移到催化剂丁 (His12).
研究的目的:
- 阐明由PAP催化的第一个脱化步骤的机制.
- 研究活性部位残留物的作用,包括His12,Arg11,Arg15,Arg79,His257和Asp258.
- 描述反应中涉及的过渡状态和能量障碍.
主要方法:
- 量子化学计算被用来建模反应机制.
- 构建了多个量子模型,其中包含了关键活性站点残留物.
- 分析的重点是过渡状态的特征和稳定能量.
主要成果:
- 初始酸盐转移的过渡状态表现出关联性特征.
- 已证实胺12 (His12) 作为核友的作用.
- 活性部位的阿尔基尼因 (Arg11,Arg15,Arg79) 稳定了过渡状态.
- 亚斯巴酸盐258 (Asp258) 拟用于作为质子捐赠体,可能由水分子辅助.
- 希斯提丁257 (His257) 降低了核友性攻击的能量屏障.
结论:
- PAP脱的第一步涉及His12.的核友攻击.
- 氨酸残留物在稳定关联过渡状态方面发挥着至关重要的作用.
- Asp258可能充当质子捐赠者,促进反应.
- 希斯257对于降低核友性攻击的激活能量很重要.
更多相关视频
12:23Phosphopeptide Enrichment Coupled with Label-free Quantitative Mass Spectrometry to Investigate the Phosphoproteome in Prostate Cancer
Published on: August 2, 2018
06:33Direct Detection of Isolevuglandins in Tissues Using a D11 scFv-Alkaline Phosphatase Fusion Protein and Immunofluorescence
Published on: July 5, 2021
相关概念视频
02:54Protein 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...
01:42Phosphoinositides 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...