与肝素结合的热力学:溶解和水结构对多糖生物功能的影响
Brenna M Knight1,2, Connor M B Gallagher1,2, Michael D Schulz1,2
1Department of Chemistry, Virginia Tech, Blacksburg, VA 24061.
概括
肝素硫酸盐和肝素调节离子 (Ca2+) 通过释放水的结合,而硫酸肝素显示出更强烈的相互作用. 这通过影响水结构和界面能量,影响生物矿物化和细胞信号.
科学领域:
- 生物化学 生化学
- 热力学是一种热力学.
- 生物矿物化 生物矿物化
背景情况:
- 肝硫酸盐是各种生物过程中必不可少的无处不在的生物大分子.
- 它们在调节离子 (Ca2+) 结合中的作用对于细胞信号传递和生物矿物化至关重要.
- 和相关多糖的Ca2+调节的热力学基础仍然不清楚.
研究的目的:
- 量化硫酸盐含量和位置如何影响Ca2+结合热力学在heparans.
- 将Ca2+结合热力学与石结晶的界面能量联系起来.
- 为了阐明Ca2+ - 多糖相互作用的热力学特征.
主要方法:
- 异热定位热量计 (ITC) 用于测量Ca2+结合热力学.
- 分析了具有不同硫酸盐修饰的肝素和肝素.
- 进行了对酸盐核化到多糖的界面能量测量.
主要成果:
- 二氧化+与肝素的结合主要是由水释放的有利热贡献驱动的.
- 氨酸与O-硫酸盐和N-硫胺基组的氨酸表现出比氨酸强约3倍的Ca2+结合.
- 较强的Ca2+结合 (较大的度) 与较高的CaCO3核化界面能量相关,表明水结构发生了变化.
结论:
- 硫酸盐组的位置和类型显著调节二+的结合亲和力和二中的热力学.
- 在Ca2+ - 多糖相互作用期间的水重组决定了与生物矿物化相关的界面特性.
- Ca2+ - 多糖相互作用共享一种共同的热力学特征,其中主导的是力-力补偿,与Ca2+ - 蛋白质结合不同.
相关概念视频
Anticoagulant Drugs: Low-Molecular-Weight Heparins
893
Hemostasis is a crucial process that prevents excessive blood loss from damaged blood vessels. It involves various mechanisms such as vasoconstriction, platelet adhesion and activation, and fibrin formation. The importance of each mechanism depends on the type of vessel injury. In contrast, thrombosis is the abnormal formation of a blood clot within the blood vessels, leading to potential complications if the clot obstructs blood flow. Thrombosis can be caused by increased coagulability of the...
893
Calmodulin-dependent Signaling
5.3K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.3K
Drug Binding to Blood Components
249
When drugs enter systemic circulation, they interact with various components of the blood, including proteins such as human serum albumin (HSA), α1-acid glycoprotein (AAG), lipoproteins, globulins, and red blood cells (RBCs).
HSA is the most abundant plasma protein and is vital in drug binding. It contains distinct drug-binding sites, with different drugs exhibiting affinity for specific sites. There are three main drug-binding domains for HSA: sites I, II, and III. These domains are...
HSA is the most abundant plasma protein and is vital in drug binding. It contains distinct drug-binding sites, with different drugs exhibiting affinity for specific sites. There are three main drug-binding domains for HSA: sites I, II, and III. These domains are...
249
Skeleton and Calcium Homeostasis
4.8K
Calcium is not only the most abundant mineral in bone but also the most abundant mineral in the human body. Calcium ions are needed for bone mineralization, tooth health, heart rate regulation and strength of contraction, blood coagulation, the contraction of smooth and skeletal muscle cells, and the regulation of nerve impulse conduction. The average calcium level in the blood is about 10 mg/dL. When the body cannot maintain this level, a person will experience hypo or hypercalcemia.
4.8K
Synthesis and Functions of Calcitonin
2.4K
Calcitonin, a vital polypeptide hormone, regulates calcium levels within body fluids. It is released by the parafollicular cells, also known as C cells, situated in the follicular epithelium of the thyroid gland. Calcitonin responds to fluctuations in blood calcium levels and the influence of gastrointestinal hormones like gastrin and cholecystokinin.
The exact mechanisms by which calcitonin operates in calcium homeostasis remain elusive, but its significance is evident in several vital...
The exact mechanisms by which calcitonin operates in calcium homeostasis remain elusive, but its significance is evident in several vital...
2.4K
Drug Distribution: Tissue Binding
3.2K
Upon entering the systemic circulation, drugs can distribute into the interstitial and intracellular fluid of various tissue cells. This distribution is facilitated by the binding of drugs to different cellular components within tissues, which may lead to drug accumulation in specific areas. Drugs bound to tissue components serve as reservoirs that release free drugs back into the system, prolonging the drug's overall action. However, this accumulation can also result in local toxicity.
For...
For...
3.2K


