药物样分子的识别,以向类似动胺的EHD4的ATPase活性
Saif Mohd1,2, Andreas Oder3, Edgar Specker3
1Structural Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
PloS one
|July 29, 2024
概括
研究人员开发了一种高通量试验,以寻找EHD4的抑制剂,这是一种参与细胞贩运和癌症的蛋白质. 发现了一种新型分子,为新的癌症疗法铺平了道路.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 分子医学是分子医学.
背景情况:
- 含有Eps15同质域的蛋白质 (EHDs) 是与胺相关的ATP酶,对内细胞膜贩运至关重要.
- EHD失调与癌症等疾病有关,但缺乏特定的抑制剂.
- 针对个别的EHD对于理解它们在细胞过程和疾病中的作用至关重要.
研究的目的:
- 建立一个高通量选试验以检测EHD4的脂质体刺激的ATPase活性.
- 为了识别针对EHD4.4的小分子抑制剂.
- 通过结构-活性关系研究指导强效EHD抑制剂的开发.
主要方法:
- 开发了一种以马六合绿色为基础的测试方法,用于监测EHD4 ATPase活性.
- 进行高通量选以识别抑制剂.
- 对已识别的抑制剂进行了结构-活性关系 (SAR) 研究.
主要成果:
- 成功建立了对EHD4脂质体刺激的ATPase活性的一种强有力的测定方法.
- 确定了一种类似药物的分子,可以抑制EHD4 ATPase活性.
- 确定用于增强抑制剂功效的关键替代位点.
结论:
- 开发的试验有效选EHD4抑制剂,适用于其它dynamin家族成员.
- 已识别的抑制剂和SAR数据为开发针对性EHD治疗提供了基础.
- 这项工作有助于进一步研究EHD在健康和疾病,特别是癌症中的功能.
相关概念视频
Pinching-off of Coated Vesicles
3.1K
Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
3.1K
ATP Synthase: Mechanism
14.3K
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
14.3K
Targets for Drug Action: Overview
6.1K
Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
6.1K


