纤维状人体氨酸β-合成酶的结构和调节
Thomas J McCorvie1,2, Douglas Adamoski3, Raquel A C Machado3
1Nuffield Department of Clinical Medicine, Centre for Medicines Discovery, University of Oxford, Oxford, OX3 7DQ, UK. thomas.mccorvie@newcastle.ac.uk.
囊氨酸β-合成酶 (CBS) 形成细丝,其活性由S-adenosyl-L-methionine (SAM) 调节. 这种聚合稳定了酶,为CBS相关疾病提供了新的治疗点.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 酶学 是一种酶学.
背景情况:
- 氨酸β-合成酶 (CBS) 是合成氨酸,氨酸和硫化的关键酶.
- 人类CBS具有一个调节域,通过S-adenosyl-L-methionine (SAM) 控制酶活性,并促进寡合化.
研究的目的:
- 阐明人类CBS调节和聚合的结构基础.
- 调查调控领域在酶活性和丝形成中的作用.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 确定了全长人体CBS的结构.
- 生物化学测试用于评估酶活性和热稳定性.
- 在PC-3细胞中进行了细胞研究,以观察对营养物质敏感的丝状结构.
主要成果:
- 人类的CBS在基底和SAM激活状态下,通过其调节域的介导,聚合成纤维.
- 在基底状态下,调节域通过阻断催化部位来抑制活性,形成低活性丝线 (3 次元/转).
- 对调节域的SAM结合会去除固体块,形成一个具有调节域和灵活的催化域核心的高活性丝 (二极管/旋转).
结论:
- CBS聚合稳定了酶,并提高了热稳定性.
- 在PC-3细胞中观察到对营养物质敏感的CBS丝,突出显示了其动态调节.
- 这些发现提供了关于CBS调节的见解,并建议针对CBS相关疾病的潜在治疗策略.
更多相关视频
15:12Purification of the Cystic Fibrosis Transmembrane Conductance Regulator Protein Expressed in Saccharomyces cerevisiae
Published on: May 10, 2014
19:16The Importance of Correct Protein Concentration for Kinetics and Affinity Determination in Structure-function Analysis
Published on: March 17, 2010
相关概念视频
Allosteric Proteins-ATCase
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
ATP Synthase: Mechanism
ATP Synthase: Structure
Cystic Fibrosis: Pathogenesis
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
Covalently Linked Protein Regulators
These groups modify specific amino acids in a protein....
Ligand Binding and Linkage
