(I) 通过两个平行路径与Zn7-MT2结合
Adyn Melenbacher1, Martin J Stillman1
1Department of Chemistry, The University of Western Ontario, London, Ontario, Canada.
Metallomics : integrated biometal science
|September 12, 2023
概括
金属氨酸-2 (MT2) 蛋白通过两个不同的途径结合铜和离子,影响金属恒温和解毒. 这项研究揭示了MT2内的特定Cu:Zn比率和结合域,这对于了解其在疾病中的作用至关重要.
科学领域:
- 生物化学 生化学
- 蛋白质组学是指蛋白质组学.
- 频谱学是一种光谱学.
背景情况:
- 金属氨酸蛋白 (MT) 对于维持铜 (Cu) 和 (Zn) 稳态以及重金属排毒至关重要.
- MT2的多样化表达和疾病相关性 (癌症,神经,呼吸系统) 强调了理解其金属化特性的重要性.
- 同位素纯度63Cu (I) 和68Zn (II) 对于解决Cu,Zn-MT2研究中的质谱复杂性至关重要.
研究的目的:
- 准确确定Cu (I) 和Zn (II) 结合MT2在生理pH时的固态度.
- 为了阐明Cu(I) 化在Zn7-MT2.2.中的并行途径.
- 为了确定各种Cu,Zn-MT2物种的形成常数 (KF),并分配光谱带.
主要方法:
- 电子喷射电离 (ESI) 质谱法用于分析Cu,Zn-MT2复合体.
- 使用质谱模拟来确定定位过程中精确的Cu:Zn比率.
- 室温光和循环二重化 (CD) 光谱为物种分配提供了并行数据.
主要成果:
- 确定了Zn7-MT2的Cu(I) 金属化的两个并行途径,产生了特定的Cu:Zn比率.
- 路径1产生了Cu5Zn5-MT2和Cu9Zn3-MT2;路径2产生了主要产品Cu6Zn4-MT2和Cu10Zn2-MT2.
- CD光谱分析表明,Cu(I) 最初与β域结合,形成Cu5Zn1或Cu6集群,离开α域与Zn4.
结论:
- 该研究使用同位素纯金属和质谱学精确量化Cu (I) 和Zn (II) 与MT2结合的固态度.
- 化通过两个不同的途径发生,导致定义的Cu,Zn-MT2物种.
- Cu(I) 首选与MT2的β域结合,从而影响整体蛋白质结构和功能.
相关概念视频
Ligand Binding and Linkage
4.8K
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
4.8K
Valence Bond Theory
8.7K
Coordination compounds and complexes exhibit different colors, geometries, and magnetic behavior, depending on the metal atom/ion and ligands from which they are composed. In an attempt to explain the bonding and structure of coordination complexes, Linus Pauling proposed the valence bond theory, or VBT, using the concepts of hybridization and the overlapping of the atomic orbitals. According to VBT, the central metal atom or ion (Lewis acid) hybridizes to provide empty orbitals of suitable...
8.7K
Metal-Ligand Bonds
20.9K
The hemoglobin in the blood, the chlorophyll in green plants, vitamin B-12, and the catalyst used in the manufacture of polyethylene all contain coordination compounds. Ions of the metals, especially the transition metals, are likely to form complexes.
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
20.9K
Ladder Diagrams: Complexation Equilibria
370
Ladder diagrams are useful for evaluating equilibria involving metal-ligand complexes. The vertical scale of the ladder diagram represents the concentration of unreacted or free ligand, pL. The horizontal lines on the scale depict the log of stepwise formation constants for metal-ligand complexes and indicate the dominant species in all the regions.
The formation constant, K1, for the formation of Cd(NH3)2+ complex from cadmium and ammonia is 3.55 × 102. Log K1 (i.e. pNH3) is 2.55, and...
The formation constant, K1, for the formation of Cd(NH3)2+ complex from cadmium and ammonia is 3.55 × 102. Log K1 (i.e. pNH3) is 2.55, and...
370
Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.3K
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
2.3K
Allosteric Proteins-ATCase
5.8K
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
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...
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...
5.8K


