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相关概念视频

Protein-protein Interfaces02:04

Protein-protein Interfaces

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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...
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Ligand Binding and Linkage00:49

Ligand Binding and Linkage

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Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked.  In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
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Conserved Binding Sites01:49

Conserved Binding Sites

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Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
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Ligand Binding Sites02:40

Ligand Binding Sites

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Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
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Protein Networks02:26

Protein Networks

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An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
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Protein Complexes with Interchangeable Parts01:57

Protein Complexes with Interchangeable Parts

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Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
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Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions
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分裂蛋白治疗平台:识别结合剂对

Christine S Nervig1, James R Gustat2, Shawn C Owen3,4,5

  • 1Department of Medicinal Chemistry, University of Utah, Salt Lake City, UT, USA.

Methods in molecular biology (Clifton, N.J.)
|September 29, 2023
PubMed
概括

研究人员开发了制造更安全的治疗蛋白质的方法. 通过分解蛋白质和使用抗体结合剂,它们可以实现条件激活,减少非目标效应,从而改善疾病治疗.

关键词:
抗体是对抗体的一种.补充 补充 补充计算建模计算建模有条件的活性.蛋白质工程是一种蛋白质工程.蛋白质开关是一个蛋白质开关.分裂-酶可以分开.

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Creating Highly Specific Chemically Induced Protein Dimerization Systems by Stepwise Phage Selection of a Combinatorial Single-Domain Antibody Library
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科学领域:

  • 生物技术是生物技术.
  • 蛋白质工程是指蛋白质工程.
  • 免疫治疗是一种免疫疗法.

背景情况:

  • 治疗性蛋白质为抗小分子药物耐药的疾病提供了先进的治疗选择.
  • 在基于蛋白质的疗法中,非标或全身活性构成了重大挑战.
  • 条件激活策略对于提高蛋白质疗法的安全性和有效性至关重要.

研究的目的:

  • 描述用于识别促进活性治疗蛋白质重构的抗体对的方法.
  • 为开发条件活性蛋白结构提供计算和实证方法.
  • 仅使用蛋白质序列数据来设计向蛋白质疗法.

主要方法:

  • 将治疗性蛋白质分解成不活跃的碎片.
  • 将蛋白质碎片与合剂结合起来,以不同的细胞表面表观为目标.
  • 使用计算和实证策略来识别功能性抗体对.
  • 评估抗体介导的近距离诱导蛋白质复制.

主要成果:

  • 证明了确定适合蛋白质复制的抗体对的方法.
  • 提供了适用于各种治疗蛋白质的一般方法.
  • 从蛋白质序列数据开始,促进了抗体对的识别.

结论:

  • 条件活性蛋白质结构可以减轻与治疗蛋白质相关的毒性.
  • 抗体介导的向和复制为局部蛋白质激活提供了一个有希望的策略.
  • 描述的方法支持开发更安全,更有效的基于蛋白质的药物.