Jove
Visualize
联系我们
JoVE
x logofacebook logolinkedin logoyoutube logo
关于 JoVE
概览领导团队博客JoVE 帮助中心
作者
出版流程编辑委员会范围与政策同行评审常见问题投稿
图书馆员
用户评价订阅访问资源图书馆顾问委员会常见问题
研究
JoVE JournalMethods CollectionsJoVE Encyclopedia of Experiments存档
教育
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab Manual教师资源中心教师网站
使用条款与条件
隐私政策
政策

相关概念视频

Allosteric Regulation01:08

Allosteric Regulation

63.0K
Allosteric regulation of enzymes occurs when the binding of an effector molecule to a site that is different from the active site causes a change in the enzymatic activity. This alternate site is called an allosteric site, and an enzyme can contain more than one of these sites. Allosteric regulation can either be positive or negative, resulting in an increase or decrease in enzyme activity. Most enzymes that display allosteric regulation are metabolic enzymes involved in the degradation or...
63.0K
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

8.6K
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
8.6K
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

2.6K
2.6K
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

3.0K
3.0K
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

6.5K
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...
6.5K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

7.3K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
7.3K

您也可能阅读

相关文章

通过共同作者、期刊和引用图与本文相关的文章。

排序
Same author

SMDNet: A Self-Training-Aware and Multi-Modal-Adaptive Deep Learning Network for Low-Data Aβ<sub>42</sub> Probe Design and Optimization.

Journal of medicinal chemistry·2026
Same author

A structurally reassembled sunflower stem pith composite sponge for prehospital temporary emergency hemostasis.

Biomaterials science·2026
Same author

A Novel Simplified Prognostic Model for 90-day Transplant-free Survival in Patients with Severe Acute Liver Injury/Acute Liver Failure.

Journal of clinical and translational hepatology·2026
Same author

IRF7 links HK1-dependent histone lactylation to fibroblast activation and cardiac fibrosis.

EMBO molecular medicine·2026
Same author

PA-X I94V mutation modulates the pathogenicity of the highly pathogenic H7N9 influenza A virus in mice and chickens.

Veterinary microbiology·2026
Same author

Organ failure-based clinical classification at onset of acute-on-chronic liver failure: a prospective multicenter cohort study.

Scientific reports·2026

相关实验视频

Updated: Jan 17, 2026

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
07:41

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators

Published on: February 20, 2018

9.4K

机器学习导航了Allosteric网络,揭示了GPCRs偏差的Allosteric调制.

Ming Kong1, Xin Chen1, Jun Mao1

  • 1College of Chemistry, Sichuan University, Chengdu 610064, China.

Journal of chemical theory and computation
|September 16, 2025
PubMed
概括

我们开发了一种机器学习策略,以了解G蛋白结合受体 (GPCRs) 的偏向性全调节器 (BAMs). 这种方法阐明了SBI-553药物如何调节NTSR1,为更安全的GPCR疗法提供了洞察力.

更多相关视频

Parallel Interrogation of &#946;-Arrestin2 Recruitment for Ligand Screening on a GPCR-Wide Scale using PRESTO-Tango Assay
09:03

Parallel Interrogation of β-Arrestin2 Recruitment for Ligand Screening on a GPCR-Wide Scale using PRESTO-Tango Assay

Published on: March 10, 2020

13.7K
Monitoring GPCR-&#946;-arrestin1/2 Interactions in Real Time Living Systems to Accelerate Drug Discovery
08:21

Monitoring GPCR-β-arrestin1/2 Interactions in Real Time Living Systems to Accelerate Drug Discovery

Published on: June 28, 2019

7.3K

相关实验视频

Last Updated: Jan 17, 2026

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
07:41

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators

Published on: February 20, 2018

9.4K
Parallel Interrogation of &#946;-Arrestin2 Recruitment for Ligand Screening on a GPCR-Wide Scale using PRESTO-Tango Assay
09:03

Parallel Interrogation of β-Arrestin2 Recruitment for Ligand Screening on a GPCR-Wide Scale using PRESTO-Tango Assay

Published on: March 10, 2020

13.7K
Monitoring GPCR-&#946;-arrestin1/2 Interactions in Real Time Living Systems to Accelerate Drug Discovery
08:21

Monitoring GPCR-β-arrestin1/2 Interactions in Real Time Living Systems to Accelerate Drug Discovery

Published on: June 28, 2019

7.3K

科学领域:

  • 计算化学和药理学计算化学和药理学
  • 分子建模和模拟分子模型
  • 机器学习在药物发现中的作用

背景情况:

  • 偏向性基调制剂 (BAM) 为选择性G蛋白结合受体 (GPCR) 疗法提供了潜力.
  • 由于其复杂性,了解BAMs的分子机制具有挑战性.
  • 目前的方法缺乏充分阐明偏向和全调制之间的相互作用的能力.

研究的目的:

  • 开发和验证一种用于研究BAM机制的新计算策略.
  • 阐明针对NTSR1.1.的特定β-阿雷斯偏差调节器 (SBI-553) 的分子机制.
  • 为分析其他GPCR系统中的偏向全调节提供一个框架.

主要方法:

  • 提出了一种机器学习导航的全性网络分析 (RMLNA) 策略.
  • 采用分子动力学 (MD) 模拟来获得偏向的形状状态.
  • 使用可解释的深度学习模型 (CNN) 识别关键残留.
  • 进行了全网络分析,以了解残留物调节效应.

主要成果:

  • 在NTSR1.1.上,RMLNA成功地揭示了SBI-553在NTSR1.1上的偏向性全调节机制.
  • SBI-553被证明可以稳定一种独特的β-arrestin偏差状态,扩大细胞内结合部位.
  • 在TM5,TM6,H8和TM7中的关键残留物被确定为β-arrestin偏差和调制的关键.
  • 分析强调了跨膜螺旋体之间的通信通路对于偏向信号的重要性.

结论:

  • 这项研究为SBI-553在NTSR1.1.上的偏向性全调节提供了新的分子洞察力.
  • 开发的RMLNA工作流提供了一种可靠和可扩展的方法,用于在不同的GPCR中研究BAM.
  • 这些发现有助于合理设计更安全,更有选择性的GPCR向治疗方法.