相关实验视频

Updated: May 28, 2025

A High-Throughput Enzyme-Coupled Activity Assay to Probe Small Molecule Interaction with the dNTPase SAMHD1

A High-Throughput Enzyme-Coupled Activity Assay to Probe Small Molecule Interaction with the dNTPase SAMHD1

Published on: April 16, 2021

全长抑制蛋白是最有效地扰乱人类dUTPase活动的

Bianka Kőhegyi^1,2, Zoé S Tóth^2,3, Enikő Gál^1,2

¹Department of Applied Biotechnology and Food Science, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3, Budapest, 111, Hungary.

Scientific reports

|February 9, 2025

概括

开发dUTPase抑制剂对于研究其作用至关重要,因为其缺乏会导致胚胎死亡. 研究人员设计了一种蛋白质抑制剂Stl,以更好地了解dUTPase在细胞中的功能.

科学领域:

生物化学生物化学
分子生物学分子生物学
酶学是一种酶学.

背景情况:

酶dUTPase是必不可少的,因为它在小鼠中被淘汰会导致胚胎死亡.
研究dUTPase的生理作用需要有效和选择性的抑制剂,以在细胞环境中进行时间和条件抑制.
之前发现的人类dUTPase的蛋白质抑制剂作为开发分子工具的基础.

研究的目的:

为研究人类dUTPase功能设计一种蛋白质抑制剂.
调查抑制的结构基础,并提高抑制剂的疗效.
阐明抑制蛋白在dUTPase活性调节中的不同域的作用.

主要方法:

确定了与人类dUTPase复合的抑制蛋白 (StlNT) 的N端域的3D晶体结构.
根据结构洞察力设计和创建StlNT的点突变,以增强抑制作用.
评估了StlNT和来自全长抑制剂的的抑制活性对人类dUTPase活性.

主要成果:

晶体结构揭示了StlNT和人类dUTPase之间的相互作用.
工程突变体显示出改善抑制的潜力.
发现全长Stl蛋白的C终端区域对于最大的酶抑制至关重要.

结论:

全长的Stl蛋白,包括其C端域,是人类dUTPase的强有力的抑制所必需的.
结构信息指导了改进的抑制剂变体的设计.
这项工作为通过条件抑制来研究dUTPase的生理作用提供了有价值的工具.

关键词:

类抑制剂类抑制剂蛋白质性抑制剂蛋白质性抑制剂基于结构的设计设计.在 dUTPase 中.

更多相关视频

Screening for Thermotoga maritima Membrane-Bound Pyrophosphatase Inhibitors

Screening for Thermotoga maritima Membrane-Bound Pyrophosphatase Inhibitors

Published on: November 23, 2019

A Semi-High-Throughput Adaptation of the NADH-Coupled ATPase Assay for Screening Small Molecule Inhibitors

A Semi-High-Throughput Adaptation of the NADH-Coupled ATPase Assay for Screening Small Molecule Inhibitors

Published on: August 17, 2019

相关概念视频

Enzyme Inhibition

Enzyme Inhibition

Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.

Allosteric Proteins-ATCase

Allosteric Proteins-ATCase

Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...