相关实验视频

Updated: Jul 5, 2025

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions

Published on: January 26, 2024

基于高斯加速分子动态模拟的Dipeptidyl化酶4和抑制性之间的相互作用机制研究

Yuyang Liu¹, Wencheng Zhao¹, Yongxin Jiang²

¹Edmond H. Fischer Signal Transduction Laboratory, School of Life Sciences, Jilin University, Changchun 130012, China.

International journal of molecular sciences

|January 23, 2024

概括

两种来自丝虫的酸,LPAVTIR和LPPEHDWR,通过稳定其活性部位或破坏其结构来抑制二基酸酶4 (DPP4),为2型糖尿病药物开发提供了新的途径.

科学领域:

生物化学和分子生物学
药理学和药物发现

背景情况:

双基化酶4 (DPP4) 抑制剂增加了隐素水平 (GLP-1,GIP),有助于控制血糖.
丝虫幼蛋白质产生了两个强大的DPP4抑制剂:Leu-Pro-Ala-Val-Thr-Ile-Arg (LPAVTIR) 和Leu-Pro-Pro-Glu-His-Asp-Trp-Arg (LPPEHDWR). 这两种抑制剂具有非常强大的作用.

研究的目的:

阐明LPAVTIR和LPPEHDWR抑制DPP4活性的分子机制.
用分子动力学模拟来研究这些产生的结合相互作用和结构变化.

主要方法:

在四个系统上进行了高斯加速分子动力学 (GaMD) 模拟:无干DPP4 (Apo),IPI结合DPP4 (阳性对照),LPAVTIR结合DPP4和LPPEHDWR结合DPP4.
分析的重点是结稳定性,活性部位相互作用,结构重组以及基质通道/腔体体积的变化.

主要成果:

拉巴维特对DPP4活性位点 (Ser630) 呈现稳定的结合,表明具有竞争性抑制.
LPPEHDWR诱导了关键α螺旋体 (残留物201-215) 的消失,破坏了活性部位并使酶失活.
这两种,与IPI对照剂相似,显著减少了基质通道和腔体积,阻碍了酶活性.

结论:

这项研究提供了对LPAVTIR和LPPEHDWR对DPP4抑制的详细机制理解.
这些发现为开发来自自然来源的新型DPP4抑制剂用于2型糖尿病治疗提供了理论基础.

关键词:

斯加速分子动力学模拟模拟在MM-PBSASA中使用.形状的变化形状的变化双基酸酶4 (DPP4) 是一种基酸酶.抑制性的抑制性.

更多相关视频

Study of Short Peptide Adsorption on Solution Dispersed Inorganic Nanoparticles Using Depletion Method

Study of Short Peptide Adsorption on Solution Dispersed Inorganic Nanoparticles Using Depletion Method

Published on: April 11, 2020

Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions

Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions

Published on: December 1, 2020

相关概念视频

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...

Protein-protein Interfaces

Protein-protein Interfaces

Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...

Glucagon-like Receptor Agonists

Glucagon-like Receptor Agonists

Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...