通过和转移差异NMR对尼古丁胺胺N-甲基转移酶和配体的结合性亲和性研究
1School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, China.
Protein and peptide letters
|August 25, 2023
概括
尼古丁胺N-甲基转移酶 (NNMT) 酶活性对健康至关重要. 这项研究表明,Y20残留物对NNMTMT至关重要.
科学领域:
- 生物化学 生物化学
- 酶学 是一种酶学.
- 结构生物学 结构生物学
背景情况:
- 尼古丁胺N-甲基转移酶 (NNMT) 在各种疾病中发挥作用,包括癌症和代谢障碍.
- 在疾病中NNMT的参与使其成为潜在的治疗目标.
- 了解NNMT的酶基质相互作用是阐明机制的关键.
研究的目的:
- 调查NNMT与其连接体,尼古丁胺胺和S-腺氨酸类固醇 (SAH) 的结合亲和力和导向.
- 确定特定的NNMT残留物在联体结合和催化活性中的作用.
主要方法:
- 使用和转移差 (STD) 核磁共振 (NMR) 技术.
- 采用局部导向的突变发生法来产生NNMT突变 (Y20F和Y20G).
- 测量了连接物与野生类型 (WT) 和突变NNMT.的结合亲缘关系 (解离常数).
主要成果:
- 野生型NNMT对尼古丁胺和SAH表现出最高的结合亲和力.
- 与WT NNMT相比,突变Y20F和Y20G的结合亲和力显著降低.
- 突变的结合亲和力变化与催化活性变化相关.
结论:
- 尼古丁胺和SAH与NNMT及其突变的结合亲和力使用STDNMR量化.
- 其余Y20对尼古丁胺和SAH与NNMT的结合方向和亲和关系至关重要.
- 这些发现为NNMT的反应机制和治疗干预的潜力提供了洞察力.
更多相关视频
10:28Measuring Interactions of Globular and Filamentous Proteins by Nuclear Magnetic Resonance Spectroscopy NMR and Microscale Thermophoresis MST
Published on: November 2, 2018
12.2K
11:44Spin Saturation Transfer Difference NMR SSTD NMR: A New Tool to Obtain Kinetic Parameters of Chemical Exchange Processes
Published on: November 12, 2016
17.9K
相关概念视频
02:18The Equilibrium Binding Constant and Binding Strength
13.0K
The equilibrium binding constant (Kb) quantifies the strength of a protein-ligand interaction. Kb can be calculated as follows when the reaction is at equilibrium:
13.0K
01:25Applications Of NMR In Biology
3.7K
Nuclear magnetic resonance (NMR) spectroscopy is a very valuable analytical technique for researchers. It has been used for more than 50 years as an analytical tool. F. Bloch and E. Purcell formulated NMR in 1946 and won the 1952 Nobel Prize in Physics for their work. Biological macromolecules such as proteins, nucleic acids, lipids, and organic molecules including pharmaceutical compounds, can be studied using this versatile tool that exploits the magnetic properties of certain nuclei.
3.7K