结构和分子基础的全调节和催化合的人类基基甲基甘氨酸胺合成酶
Nandini Sharma1, Weijie Zhou2,3, Jarrod B French4
1The Hormel Institute, University of Minnesota, Austin, MN, 55912, USA.
Nature communications
|February 13, 2026
概括
研究人员揭示了氨酸生物合成中的一个关键酶 - - 酸基甲基糖胺氨酸合成酶的结构. 这为癌症代谢和潜在的新药标提供了洞察力.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 代谢途径 代谢途径
背景情况:
- 纯氨酸核酸对所有细胞功能至关重要.
- 新生生物合成是关键的代谢途径,在癌症中经常发生改变.
- 这一途径是各种治疗策略的验证目标.
研究的目的:
- 使用冷电子显微镜阐明人类基基胺酸合成酶 (PFAS) 的结构.
- 了解酶的机制,包括拟议的胺基酸中间体和氨通道.
- 为了研究酶域内的全调节和催化合.
主要方法:
- 电子显微镜 (cryo-EM) 用于高分辨率的结构确定.
- 生物化学试验分析酶活性和调节.
- 多种酶状态和中间体的结构分析.
主要成果:
- 确定了人类PFAS的冷-EM结构,捕获了一种拟议的胺酸中间体.
- 提供了连接谷氨胺酶和合成酶活性位点的氨通道的结构证据.
- 揭示了分子特征和结构动力学,负责全调节和域合.
结论:
- 这项研究解决了关于PFAS在purinosome中的作用的关键机制问题.
- 对PFAS的结构洞察力为开发针对 purin生物合成的新疗法提供了基础.
- 了解这种中央酶对于推进癌症,抗病毒和免疫调节疗法至关重要.
相关概念视频
Allosteric Regulation
63.5K
Allosteric regulation of enzymes occurs when the binding of an effector molecule to a site that is different from the active site causes a change in the enzymatic activity. This alternate site is called an allosteric site, and an enzyme can contain more than one of these sites. Allosteric regulation can either be positive or negative, resulting in an increase or decrease in enzyme activity. Most enzymes that display allosteric regulation are metabolic enzymes involved in the degradation or...
63.5K
ATP Synthase: Structure
15.8K
ATP synthase or ATPase is among the most conserved proteins found in bacteria, mammals, and plants. This enzyme can catalyze a forward reaction in response to the electrochemical gradient, producing ATP from ADP and inorganic phosphate. ATP synthase can also work in a reverse direction by hydrolyzing ATP and generating an electrochemical gradient. Different forms of ATP synthases have evolved special features to meet the specific demands of the cell. Based on their specific feature, ATP...
15.8K
Regulated Protein Degradation
8.9K
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
8.9K
Cooperative Allosteric Transitions
8.9K
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...
8.9K
Cooperative Allosteric Transitions
2.7K
2.7K
Chromatin Structure Regulates pre-mRNA Processing
8.3K
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
8.3K


