对人类免疫调节性甲素S的动态形态转换和活性位点可塑性的新见解
Durga Geetha1, B A Aysha Hameeda2, Deepthi Jose3
1Department of Bioscience and Engineering, National Institute of Technology Calicut, Calicut, Kerala, India.
Proteins
|May 26, 2025
概括
了解甲素S (CatS) 的可塑性是药物发现的关键. 这项研究揭示了特定的氨基酸运动如何调节CatS结构,影响药物结合,并可能有助于选择性药物设计用于自身免疫性疾病.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 药物发现 药物发现 药物发现
背景情况:
- 甲素S (CatS) 是一种囊蛋白酶,参与自身免疫和炎症性疾病.
- 它的连接物结合点可塑性对于药物发现至关重要,但其构造格局尚未完全理解.
研究的目的:
- 研究控制CatS结构和功能可塑性的原子级相互作用.
- 阐明 CatS 形态状态之间的动态转换机制.
主要方法:
- 在CatS活性位点裂内对原子级相互作用的分析.
- 研究侧链运动和残留物之间的相互作用.
主要成果:
- Phe211,Phe70和Tyr118的脚运动调节了CatS S2口袋形状 (开放/关闭状态).
- Phe70作为S2口袋大小和小分子结合的关键调节者.
- 状态之间的过渡形成了三个不同的半封闭子状态,受非共价相互作用的影响.
- 通过对Phe70或Phe211链运动进行绝缘阻碍,可以阻止连接物结合.
结论:
- Phe211,Phe70和Tyr118的合作侧链运动决定了连接体的宿舍和特异性.
- 这些发现可以指导选择性小分子药物的设计,针对特定的CatS结构状态,用于治疗炎症和自身免疫性疾病.
相关概念视频
Catenins
3.0K
Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...
3.0K
Protein Folding
11.2K
Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
11.2K
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
Intrinsically Disordered Proteins
19.2K
Intrinsically disordered proteins are a group of proteins that do not fold into specific three-dimensional structures. Their structural flexibility allows them to complement ordered proteins to perform functions that are inaccessible to rigid structures. They are more common in eukaryotes than prokaryotes and may either be exclusively intrinsically disordered or hybrid proteins, consisting of a mix of ordered and disordered regions. The absence of a rigid structure in these proteins can be...
19.2K
Ligand Binding and Linkage
5.5K
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...
5.5K
Caspases
13.7K
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
13.7K


