腺酸酶特定单体的结合机制
Ibuki Nakamura1, Hiroshi Amesaka2, Satoshi Nagao3
1Division of Materials Science, Nara Institute of Science and Technology (NAIST), Ikoma, Nara, Japan.
FEBS letters
|May 22, 2025
概括
单体调节酶的功能. 这项研究表明CL-1通过度结合腺酸激酶 (Adk),而OP-4通过度结合,揭示了不同的单体结合机制.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 蛋白质工程是指蛋白质工程.
背景情况:
- 单体是模仿抗体的工程蛋白质,用于通过特定相互作用调节蛋白质功能.
- 腺酸酶 (Adk) 是细胞能量代谢中的关键酶,存在于不同的结构状态.
研究的目的:
- 阐明两种单体CL-1和OP-4与腺酸激酶 (Adk) 结合的不同结合机制.
- 描述单体结合Adk.的热力学和结构后果.
主要方法:
- 异热定位热量计 (ITC) 用于确定结合热力学.
- 在原子层面上可视化蛋白质-蛋白质相互作用的X射线晶体学.
- 核磁共振 (NMR) 光谱 (1H-15N 2D NMR,31P-NMR) 用于评估形状变化.
主要成果:
- 特定于CLOSED Adk构造的CL-1,通过键和子-π相互作用的能驱动过程结合,而不会改变Adk骨干结构.
- 特定于OPEN Adk形状的OP-4,表现出由驱动的结合.
- OP-4结合诱导Adk的形状变化,但仍然保留了基质访问.
结论:
- 单体表现出多样化的结合策略,在热力学驱动因素和对酶的结构影响上有所不同.
- 了解这些多样化的机制是设计有效的蛋白质-蛋白质相互作用调节器的关键.
更多相关视频
11:02Genetic Encoding of a Non-Canonical Amino Acid for the Generation of Antibody-Drug Conjugates Through a Fast Bioorthogonal Reaction
Published on: September 14, 2018
7.7K
11:23Characterization at the Molecular Level using Robust Biochemical Approaches of a New Kinase Protein
Published on: June 30, 2019
6.1K
相关概念视频
Receptor Tyrosine Kinases
12.0K
Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
12.0K
Transducer Mechanism: Enzyme-Linked Receptors
2.3K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
2.3K
Antibody Structure
58.7K
Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
58.7K
Amplifying Signals via Enzymatic Cascade
8.2K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
8.2K
Antibody Structure and Classes
723
Antibodies, also known as immunoglobulins, are produced by B cells in response to foreign substances, such as bacteria and viruses. These proteins are critical for recognizing and neutralizing these substances, protecting the body from potential harm.
The basic structure of an antibody consists of four protein chains: two identical heavy chains and two identical light chains. These chains are held together by disulfide bonds and other non-covalent interactions, forming a Y-shaped structure.
The basic structure of an antibody consists of four protein chains: two identical heavy chains and two identical light chains. These chains are held together by disulfide bonds and other non-covalent interactions, forming a Y-shaped structure.
723
