叶酸受体对叶酸的分子识别的结构基础
Chen Chen1, Jiyuan Ke, X Edward Zhou
1Program for Structural Biology and Drug Discovery, Van Andel Research Institute, 333 Bostwick Avenue North East, Grand Rapids, Michigan 49503, USA.
Nature
|July 16, 2013
概括
研究人员确定了与叶酸结合的叶酸受体α (FRα) 的晶体结构. 这种结构揭示了FRα如何结合叶酸,为开发向癌症治疗提供了一个模板.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 在瘤学瘤学.
背景情况:
- 叶酸受体 (FRα,FRβ,FRγ) 是细胞表面的糖蛋白,对叶酸的吸收至关重要.
- 在许多癌症中,FRα表达的升高推动了瘤的生长,使其成为治疗点.
研究的目的:
- 阐明叶酸与叶酸受体α (FRα) 结合的结构基础.
- 为设计新型FRα向癌症药物提供一个结构模板.
主要方法:
- 在2.8 Å分辨率下确定了人体FRα与叶酸复合的晶体结构.
主要成果:
- FRα具有球状结构,有八个二硫化键和一个深厚的,保存的叶酸结合口袋.
- 叶酸的酸基被埋葬,而谷氨酸基暴露,使药物结合成为可能.
- 广泛的受体-连接体相互作用解释了高叶酸结合亲和力.
结论:
- 确定的FRα-叶酸结构为叶酸结合提供了关键的见解.
- 这些结构信息可以指导开发更具体,更有效的针对叶酸受体的治疗方法.
相关概念视频
Conserved Binding Sites
4.1K
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...
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...
4.1K
Ligand Binding and Linkage
4.4K
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...
4.4K
Association Areas of the Cortex
10.2K
Association areas are regions of the cerebral cortex that do not have a specific sensory or motor function. Instead, they integrate and interpret information from various sources to enable higher cognitive processes such as memory, learning, and decision-making. Some key association areas include the following:
Prefrontal Association Area: This area is located in the frontal lobe and is involved in planning, decision-making, and moderating social behavior. It connects with primary motor areas,...
Prefrontal Association Area: This area is located in the frontal lobe and is involved in planning, decision-making, and moderating social behavior. It connects with primary motor areas,...
10.2K


