相关实验视频
Updated: Dec 30, 2025
09:54
A Model to Simulate Clinically Relevant Hypoxia in Humans
Published on: December 22, 2016
9.2K
在使用多尺度模拟的低氧感应酸中分子氧气扩散的机制
Carmen Domene1,2,3, Christian Jorgensen2, Christopher J Schofield1
1Chemistry Research Laboratory, Mansfield Road , University of Oxford , Oxford OX1 3TA , United Kingdom.
Journal of the American Chemical Society
|January 16, 2020
概括
低氧诱导的转录因子 (HIF) 调节动物对低氧的反应. 这项研究揭示了二氧化物如何到达PHD2酶活性部位,这对HIF调节和检测氧气水平至关重要.
科学领域:
- 生物化学和分子生物学
- 结构生物学
- 计算生物学
背景情况:
- 细胞对缺氧 (低氧) 的反应主要由缺氧诱导的转录因子 (HIF) 介导.
- 酸酶域酶 (PHD) 是关键的氧气传感器,通过酸化调节酸的稳定性.
- PHD的独特动力学,包括高氧化Km和缓慢的反应速度,对于它们的传感功能至关重要.
研究的目的:
- 研究人类PHD2酶活性部位的二氧化物扩散和结合机制.
- 了解PHD2与二氧化物的缓慢反应动力学的化学基础.
- 阐明二氧化物结合在PHD低氧感应能力中的作用.
主要方法:
- 采用了多尺度计算方法,将经典的原子分子动力学 (MD) 模拟与QM/MM轨迹结合起来.
- 在PHD2.Fe(II).2OG.HIF基质复合体内研究了二氧化物运输和结合.
- 开发了二氧化物:PHD2相互作用的扩散反应模型.
主要成果:
- 确定了由酶和基质元素形成的单一,明确的氧气运输道到PHD2活性部位.
- 提供了控制二氧化物扩散和PHD2反应的速率常数的估计值.
- 提供了PHD2与氧气的缓慢反应动力学的化学见解,表明可逆的氧气结合对低氧感应至关重要.
结论:
- 氧气与PHD2的运输和可逆结合对于其低氧感应功能至关重要.
- 对于不同HIF-α基质,PHD2对氧水平的敏感性可能有所不同.
- 信号降解的HIF-α prolyl化程度受到散装和结合的二氧化物之间的平衡的影响.
相关概念视频
01:23Hypoxia
1.8K
Hypoxia is a medical condition characterized by an inadequate oxygen supply to body tissues. It typically manifests as a bluish discoloration of the skin and mucosae, especially in fair-skinned individuals, when hemoglobin (Hb) saturation drops below 75%.
Types of Hypoxia
There are four primary types of hypoxia, each resulting from a different cause:
1. Anemic hypoxia: This type occurs due to insufficient oxygen delivery caused by a lack of red blood cells (RBCs) or RBCs with abnormal or...
Types of Hypoxia
There are four primary types of hypoxia, each resulting from a different cause:
1. Anemic hypoxia: This type occurs due to insufficient oxygen delivery caused by a lack of red blood cells (RBCs) or RBCs with abnormal or...
1.8K
01:27Oxygen Transport in the Blood
5.5K
Hemoglobin (Hb) is a crucial molecule in the human body, consisting of four polypeptide chains, each bound to an iron-containing heme group. This unique structure enables hemoglobin to bind to oxygen, with each molecule capable of combining with four molecules of oxygen, leading to rapid and reversible oxygen loading. When fully loaded with oxygen, it is called oxyhemoglobin, while hemoglobin that has released oxygen is called reduced hemoglobin or deoxyhemoglobin. As hemoglobin binds oxygen,...
5.5K
01:58Cooperative Allosteric Transitions
8.6K
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...
8.6K
01:29Oxygen Requirements and Growth Patterns
1.1K
Microorganisms exhibit diverse oxygen requirements and growth patterns driven by their metabolic strategies and environmental adaptations. Oxygen, while essential for many organisms, can also be toxic under certain conditions, shaping how microorganisms grow and survive.Oxygen Requirements of MicroorganismsMicroorganisms are classified based on their ability to use or tolerate oxygen:● Obligate aerobes like Mycobacterium tuberculosis need oxygen for energy production, as it serves as the...
1.1K